Jump to content

Moclobemide

From Wikipedia, the free encyclopedia
(Redirected from Aurorix)

Moclobemide
Clinical data
Trade namesAmira, Aurorix, Clobemix, Depnil, Manerix, others
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability55–95% (increases with repeat administration)[2][3]
Protein binding50%[3][4]
MetabolismLiver[7][5]
Elimination half-life1–2 hours,[5] 4 hours (elderly)[3][6]
ExcretionKidney, Faecal (<5%)[4]
Identifiers
  • 4-chloro-N-(2-morpholin-4-ylethyl)benzamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.163.935 Edit this at Wikidata
Chemical and physical data
FormulaC13H17ClN2O2
Molar mass268.74 g·mol−1
3D model (JSmol)
  • Clc1ccc(cc1)C(=O)NCCN2CCOCC2
  • InChI=1S/C13H17ClN2O2/c14-12-3-1-11(2-4-12)13(17)15-5-6-16-7-9-18-10-8-16/h1-4H,5-10H2,(H,15,17) checkY
  • Key:YHXISWVBGDMDLQ-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Moclobemide, sold under the brand names Amira, Aurorix,[8] Clobemix, Depnil and Manerix[9] among others, is a reversible inhibitor of monoamine oxidase A (RIMA) drug primarily used to treat depression and social anxiety.[10][11][12] It is not approved for use in the United States,[13] but is approved in other Western countries such as Canada, the UK[12] and Australia.[14] It is produced by affiliates of the Hoffmann–La Roche pharmaceutical company. Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.

No significant rise in blood pressure occurs when moclobemide is combined with amines such as tyramine-containing foods or pressor amine drugs, unlike with the older irreversible and non-selective monoamine oxidase inhibitors (MAOIs), which cause a severe rise in blood pressure with such combination.[10] Due to the lack of anticholinergic, cardiovascular, cognitive and psychomotor impairments moclobemide is advantageous in the elderly as well as those with cardiovascular disease.[10]

Moclobemide was first introduced for medical use in 1989.[15][16]

Medical uses

[edit]

Reversible selective MAOIs such as moclobemide are underprescribed due to the misconception that the side effect profiles are analogous to that of the irreversible and non-selective MAOIs.[17] MAOIs such as moclobemide are reported to have a relatively fast onset of action compared to other antidepressant drug classes,[18] and have good long-term tolerability in terms of side effects.[19]

Tolerance does not seem to occur; research has found that moclobemide retains its beneficial therapeutic properties in depression for at least a year.[20]

  • Unipolar depression – Moclobemide has demonstrated effectiveness and efficacy in the treatment and management of major depressive disorder,[21] with both endogenous and non-endogenous depression responding; in addition moclobemide has a fast onset of action compared to other antidepressants and is significantly more tolerable than the tricyclic antidepressants.[22] Due to a good safety profile and low incidence of side effects moclobemide is likely to have a high level of acceptability by individuals suffering from depression.[23] Higher doses (>450 mg/day) may be more effective in severe depression, while patients treated with a lower dose tend to respond less well than those treated with tricyclic antidepressants.[24]
Psychotic depression, unipolar endogenous depression, melancholic depression, retarded depression, agitated depression and neurotic depression all respond to moclobemide,[25] as does atypical depression.[26] Unipolar endogenous depression is reported to have the best response to moclobemide therapy.[27][28] Individuals suffering from depression who are given moclobemide are twice as likely to improve on moclobemide than on placebo.[29] A concern of antidepressant adverse effects is sexual dysfunction; however, moclobemide has been found to actually increase libido and improve impaired erection, ejaculation and orgasm.[30] Cardiovascular toxicity is a concern with antidepressants such as tricyclic antidepressants as well as the irreversible MAOIs; when cardiovascular toxicity is a concern, SSRIs or the reversible MAOIs such as moclobemide are an option as they lack or have a significantly reduced level of cardiovascular toxicity in terms of adverse effect as well as in overdose.[31]
The effectiveness of moclobemide in agitated depression is equivalent to that of imipramine and sedative antidepressants such as amitriptyline, mianserin and maprotiline. The therapeutic response in agitated depressive individuals is similar to that seen in non-agitated depression; however, a past history of use of antidepressants reduces the chance of successful therapeutic response. The addition of a benzodiazepine to moclobemide therapy has not been found to be of benefit in this population group.[32] Moclobemide has better tolerability compared to TCAs.[33][34]
  • Dysthymia – moclobemide has been found to be effective in the treatment and management of this depressive disorder.[35]
  • Social phobia – Moclobemide has been found to be effective for the treatment of social anxiety disorder in both short and long-term placebo controlled clinical trials.[36] Moclobemide is effective but not as effective as the irreversible MAOIs in the treatment of social phobia.[37] Maximal benefits can take 8–12 weeks to manifest.[38] There is a high risk of treatment failure if there is co-morbid alcohol use disorder, however.[39] The Australian Medicines Handbook lists social phobia as an accepted but not a licensed indication.[11] The use of moclobemide in the treatment of social anxiety disorder has given mixed results with a tendency of response at higher doses (>300 mg/d) compared with placebo.[40]
  • Smoking cessation – Moclobemide has been tested in heavy dependent smokers against placebo based on the theory that tobacco smoking could be a form of self-medicating of major depression,[41] and moclobemide could therefore help increase abstinence rates due to moclobemide mimicking the MAO-A inhibiting effects of tobacco smoke. A 2023 Cochrane review[42] found only one 1995 trial[41] studying the effects of moclobemide on smoking cessation, it was administered for 3 months and then stopped; at 6 months follow-up it was found those who had taken moclobemide for 3 months had a much higher successful quit rate than those in the placebo group. However, at 12-month follow-up the difference between the placebo group and the moclobemide group was no longer significant.
  • Panic disorder – moclobemide is useful in the treatment and management of panic disorder.[43] Panic disorder is mentioned as an accepted but unlicensed indication in the Australian Medicines Handbook.[11]
  • ADHD – Two small studies assessing the benefit of moclobemide in people with attention deficit disorder found that moclobemide produced favourable results.[25]
  • Fibromyalgia – moclobemide has been found to improve pain and functioning in this group of people.[44]

Similar to other MAOIs, reversible MAOIs such as moclobemide may also be effective in a range of other psychiatric disorders.[25][45][which?] Menopausal flushing may also respond to moclobemide.[46]

In efficacy studies for the treatment of major depressive disorder, moclobemide has been found to be significantly more effective than placebo, as effective as the tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), and somewhat less effective than the older, irreversible MAOIs phenelzine and tranylcypromine. In terms of tolerability, however, moclobemide was found to be comparable to the SSRIs and better tolerated than the TCAs and older MAOIs.[13] There is some evidence that moclobemide on its own or in combination with other antidepressants such as SSRIs is also effective for treatment resistant depression and that the combination can be administered without the development of serotonin syndrome; however, further research is needed before such a combination can be recommended.[10][47] Follow-up studies show that ongoing use of antidepressants leads to continuing improvement in depression over time; and also have demonstrated that moclobemide retains its therapeutic efficacy as an antidepressant for at least a year. This long-term efficacy is equivalent to that seen with other antidepressant classes.[17]

People on irreversible MAOIs have to discontinue these antidepressants two weeks before general anesthesia, however, the use of moclobemide, due to its reversible nature, would allow such patients to possibly continue antidepressant therapy.[48][49]

A dexamethasone suppression test (DST) and plasma and urine methoxyhydroxyphenylglycol (MHPG) test can be used to estimate who is likely to respond to moclobemide antidepressant therapy.[50]

Pregnancy and lactation

[edit]

The doses of moclobemide in breast milk are very low (0.06% of moclobemide being recovered in breast milk) and therefore it has been concluded that moclobemide is unlikely to have any adverse effect on a suckling baby.[9]

Children

[edit]

Use in children is not recommended as there is insufficient data to assess safety and efficacy in these patients.[11][12]

Elderly

[edit]

Reversible MAOIs such as moclobemide may have advantages in the treatment of depression associated with Alzheimer's disease due to its effect on noradrenaline.[51] Cognitive impairments have been found to improve in people with dementia when depression is treated with moclobemide.[25] Due to its superior safety profile, moclobemide has been recommended as a first line agent for the treatment of depression in the elderly.[52] Due to the side effect profile of moclobemide, it may be a better option for this sub group of people than other antidepressants.[53] Research has found evidence that moclobemide may be able to counter anti-cholinergic (Scopolamine) induced cognitive impairments thus making moclobemide a good choice in the depression in the elderly and those with dementia.[54]

Adverse effects

[edit]

The incidence of adverse events is not correlated with age; however, adverse events occur more often in females than in males.[55] Moclobemide is regarded as a generally safe antidepressant and due to its favorable side effect profile, it can be considered a first-line therapeutic antidepressant.[56] The rate of incidence of side effects of moclobemide is low,[23] with insomnia, headache and dizziness being the most commonly reported side effects in the initial stages of therapy with moclobemide.[57] Moclobemide, even at high doses of 600 mg, does not impair the ability to drive a motor vehicle.[9][2] The tolerability of moclobemide is similar in women and men and it is also well tolerated in the elderly.[58] Moclobemide has been found to be superior to tricyclic and irreversible MAOI antidepressants in terms of side effects, as it does not cause anticholinergic, sedative or cardiovascular adverse effects.[10][2]

Unlike the irreversible MAOIs there is no evidence of liver toxicity with moclobemide.[59] Moclobemide has a similar efficacy profile compared to other antidepressants while being superior to the classic MAOIs and the tricyclics in terms of tolerance and safety profile.[60] Moclobemide has little effect on psychomotor functions.[61] Other side effects include nausea, insomnia, tremor and lightheadedness; orthostatic hypotension (dizziness upon standing) is uncommon even among the elderly.[13] Behavioural toxicity or other impairments relating to everyday living does not occur with moclobemide, except that in doses of 400 mg or higher peripheral reaction time may be impaired.[62] Peripheral oedema has been associated with moclobemide.[63]

Some of the side effects are transient and disappear within 2 weeks of treatment.[64] Serious fatigue, headache, restlessness, nervousness and sleep disturbances have been described as side effects from moclobemide therapy.[65] A paradoxical worsening of depression has been reported in some individuals in several studies,[66] and reports of suicide or suicidal ideation have been reported as a rare adverse effect of moclobemide.[67] Overall, antidepressants decrease the risk of suicide.[68] Moclobemide is believed to have only small proconvulsant effects;[69] however, rarely seizures may occur.[70] Hypertension has been reported to occur very rarely with moclobemide therapy.[13]

Moclobemide is relatively well tolerated. The following are the potential adverse effects and their respective incidences:[14][71]

Common (>1% incidence) adverse effects
  • Nausea
  • Dry mouth
  • Constipation
  • Diarrhea
  • Insomnia
  • Dizziness
  • Anxiety
  • Restlessness
Uncommon/Rare (<1%) adverse effects
  • Difficulties falling asleep
  • Nightmares and vivid dreams
  • Hallucinations
  • Memory disturbances
  • Confusion
  • Disorientation
  • Delusions
  • Increased depression
  • Excitation/irritability
  • Hypomania
  • Mania
  • Aggressive behaviour
  • Apathy
  • Tension
  • Suicidal ideation
  • Suicidal behaviour
  • Migraine
  • Extrapyramidal effects
  • Tinnitus
  • Paraesthesia
  • Dysarthria
  • Heartburn
  • Gastritis
  • Tympany
  • Indigestion
  • Hypertension
  • Bradycardia
  • Extrasystoles
  • Angina/chest pain
  • Phlebetic symptoms
  • Flushing
  • Exanthema/rash
  • Allergic skin reaction
  • Itching
  • Gingivitis
  • Stomatitis
  • Dry skin
  • Conjunctivitis
  • Pruritus
  • Urticaria
  • Disturbances of micturition (dysuria, polyuria, tenesmus)
  • Metrorrhagia
  • Prolonged menstruation
  • General malaise
  • Skeletal/muscular pain
  • Altered taste sensations
  • Hot flushes/cold sensation
  • Photopsia
  • Dyspnoea
  • Visual disturbances
  • Increased hepatic enzymes without associated clinical sequelae.

Contraindications

[edit]

Avoid use in:[11]

and caution is recommended in:[12]

Drug Interactions

[edit]

Moclobemide has fewer interactions than irreversible MAOIs. Cimetidine however, causes a significant rise in moclobemide levels and therefore if the combination is used, lower doses of moclobemide have been recommended.[72] There is little increase in the effects of alcohol when combined with moclobemide[72] and, in fact, moclobemide causes a reduction in alcohol-related impairments.[61] Moclobemide also interacts with pethidine/meperidine,[73] and dextropropoxyphene.[60] Ephedrine in combination with moclobemide increases the risk of cardiovascular adverse effects.[74] Moclobemide is also likely to interact with warfarin.[75] The combination of moclobemide with prescription or over the counter sympathomimetic drugs is not recommended due to the potential of significant drug interactions.[76]

Serotonin syndrome has been reported when moclobemide has been taken in combination with other serotonin enhancing drugs; however, due to moclobemide's reversible MAO inhibition, serotonin syndrome is significantly less likely to occur with moclobemide than with older irreversible MAOIs.[11][77][78] Serotonin syndrome has been reported when trazodone was abruptly replaced with moclobemide.[79] Taking at the same time or starting moclobemide too soon after discontinuing clomipramine or serotonin reuptake inhibitors such as SSRIs may result in the development of a serotonin syndrome.[60][80] SNRIs such as venlafaxine in combination with moclobemide have also been associated with serotonin syndrome.[81] Cimetidine causes a doubling of the blood plasma levels of moclobemide.[9] Blood plasma levels of trimipramine and maprotiline and possibly other tricyclic antidepressants increase when used in combination with moclobemide and may require dosage adjustments if the combination is used for treatment resistant depression.[82] The elimination of zolmitriptan is reduced by moclobemide and if the combination is used, a dosage reduction of zolmitriptan is recommended.[83] Moclobemide reduces the metabolism of dextromethorphan.[84] Moclobemide may decrease metabolism of diazepam, omeprazole, proguanil, propranolol and others due to inhibition of CYP2C19.[85]

Dietary

Irreversible MAOIs can cause unpleasant and occasionally dangerous side effects such as a hypertensive crises after intake of food or drink containing indirectly acting sympathomimetic amines such as tyramine. This is sometimes referred to as the 'cheese effect'. These side effects are due to irreversible inhibition of MAO in the gut and vasomotor neurones. However, the reversible MAOI antidepressants such as moclobemide have a very different side effect profile in this regard.[9] The reversible binding to MAO-A by moclobemide allows amines such as tyramine to displace moclobemide from MAO-A allowing its metabolism and removing the risk of a hypertensive crisis that occurs with irreversible MAO inhibition.[86] Of 2300 people in multiple clinical trials who were treated with moclobemide in doses up to 600 mg with no dietary restrictions, none experienced a tyramine-mediated hypertensive reaction.[58] As the pressor effect of moclobemide is so low, dietary restrictions are not necessary in people eating a normal diet, in contrast to irreversible MAOIs.[10] However, some rare cheeses that have a high tyramine level may possibly cause a pressor effect and require caution.[87] The potentiation of the pressor effect of tyramine by moclobemide is only one seventh to one tenth of that of irreversible MAOIs.[88] In order to minimize this potentiation, postprandial administration (taken after meals) of moclobemide is recommended.[9] The combined use of moclobemide and selegiline requires dietary restrictions as the combination can lead to increased sensitivity to the pressor effect of foods containing tyramine.[89]

While moclobemide or the irreversible MAO-B selective inhibitor selegiline taken alone has very little pressor effect, and requires no dietary restriction, the combination of selegiline with moclobemide leads to a significant enhancement of the pressor effect and such a combination requires dietary restriction of foods containing high amounts of tyramine.[90] The combination of moclobemide and a reversible MAO-B inhibitor requires tyramine dietary restrictions.[91]

Overdose

[edit]

Moclobemide is considered to be less toxic in overdose compared to older antidepressants, such as the tricyclic antidepressants and the irreversible and non-selective MAOIs,[10] making it a safer antidepressant in the elderly or people with physical disorders.[2] Of 18 people who overdosed on moclobemide during clinical trials, all recovered fully and moclobemide was judged to be safe for inpatient as well as outpatient use.[92] Intoxications with moclobemide as single agent are usually mild; however, when combined with tricyclic or SSRI antidepressants the overdose is much more toxic and potentially fatal.[93][94] Moclobemide, is preferred by doctors for patients who are at risk of suicide, due to moclobemide's low toxicity in overdose.[95] Patients with mixed intoxications (e.g. with other CNS active drugs) may show severe or life-threatening symptoms and should be hospitalized. Treatment is largely symptomatic and should be aimed at maintenance of the vital functions.

Withdrawal and tolerance

[edit]

Withdrawal symptoms appear to be very rare with moclobemide compared to other antidepressants[citation needed]; a single report of relatively mild flu-like symptoms persisting for 7 days after rapid reduction of high dose moclobemide therapy has been reported in one patient.[96] Withdrawal of moclobemide causes a rebound in REM sleep.[9]

Moclobemide does not seem to prevent withdrawal symptoms from serotonin reuptake inhibitors.[97]

Discontinuation of moclobemide is recommended to be done gradually to minimise side effects (e.g. rapid return of condition being treated and/or the appearance of withdrawal symptoms). Tolerance to the therapeutic effects has been reported in a small number of users of MAOIs including moclobemide.[17]

Pharmacology

[edit]
A picture of 150 mg tablets of the reversible MAOI drug moclobemide, brand name Aurorix.

Moclobemide is a benzamide,[13] derivative of morpholine,[98] which acts pharmacologically as a selective, reversible inhibitor of monoamine oxidase-A (RIMA),[10] a type of monoamine oxidase inhibitor (MAOI), and increases levels of norepinephrine (noradrenaline), dopamine, and especially serotonin[9][99] in neuronal cells as well as in synaptic vesicles; extracellular levels also increase which results in increased monoamine receptor stimulation and suppression of REM sleep, down regulation of beta-3 adrenergic receptors. Moclobemide's primary action is to disable MAO-A enzymes from decomposing norepinephrine, serotonin, and dopamine which results in a rising level of these neurotransmitters. Although it has been estimated that a single 300 mg dose of moclobemide inhibits 80% of monoamine oxidase-A (MAO-A) and 20-30% of MAO-B,[100] studies evaluating brain occupancy of MAO-A enzymes have shown dosages of 600 mg to only inhibit 74% of MAO-A enzymes[101] and dosages in the 900–1200 mg range to inhibit slightly less MAO-A than phenelzine (Nardil) at 45–60 mg;[102] subsequently, it is highly plausible that reports of lower efficacy[103] could be largely or entirely the consequence of conservative dosage guidelines rather than the pharmacological properties of the drug. Previously, it was widely reported that both MAO-A and MAO-B enzymes were responsible for the metabolism of dopamine; however, new research suggests that MAO-B enzymes are involved in the generation of GABA and not the degradation of dopamine.[104] There is also some evidence of moclobemide possessing neuroprotective properties in rodent models.[9] There is no cumulative effect of moclobemide centrally when taken long-term.[9] With long-term use of moclobemide, there is a significant down-regulation of B-adrenoceptors.[9] Single or repeated dosing with 100–300 mg of moclobemide leads to a reduction in deaminated metabolites of amines such as 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethylglycol as well as 5-HIAA. Excretion of homovanillic acid and vanillylmandelic acid via urine is also reduced. There is also a temporary increase in prolactin during initial intake of 100–300 mg of moclobemide.[9] L-dihydroxyphenylalanine is also reduced.[105] Inhibition of the serotonin metabolite is less pronounced than the norepinephrine metabolite which suggests there are other major metabolic pathways for serotonin other than MAO-A.[106]

It has been described as a 'slow binding inhibitor', whereby conformational changes to either moclobemide or the enzyme to MAO-A slowly form a more tightly bound complex, resulting in the non-competitive MAO inhibition by moclobemide.[9] With three times daily dosing the inhibition on MAO-A was relatively constant with moclobemide.[107] The MAO inhibition of moclobemide lasts about 8–10 hours and wears off completely by 24 hours after dosing.[9][99] The inhibition of MAO-A by moclobemide is 10 times more potent than the irreversible MAOI phenelzine and approximately equivalent to tranylcypromine and isocarboxazid.[9]

Moclobemide increases levels of extracellular monoamines and decreases levels of their metabolites in rat brains; tolerance to these effects does not seem to occur with chronic use of moclobemide. Moclobemide lacks anticholinergic effects and cognitive impairments can be improved by moclobemide.[108] Moclobemide suppresses the unstimulated release of certain proinflammatory cytokines which are believed to be involved in the pathophysiology of major depression and stimulates the release of anti-inflammatory cytokines.[109] Long-term treatment with moclobemide leads to an increase in cyclic adenosine monophosphate (cAMP) binding to cAMP-dependent protein kinase (PKA).[110]

Moclobemide is chemically unrelated to irreversible MAOI antidepressants and only has a very weak pressor effect of orally administered tyramine.[111] In humans, the n-oxide metabolites of moclobemide and moclobemide itself are the compounds that produce most of the inhibition of MAO-A; other metabolites are significantly less potent than the parent compound.[9]

In healthy people moclobemide has a relatively small suppressing effect on REM sleep; in contrast, depressed people who have been treated with moclobemide, progressively show improved sleep over a 4-week period, with an increase in stage 2 non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep.[9] There have been conflicting findings with regard to moclobemide altering cortisol levels and whether moclobemide increases growth hormone levels.[9] Testosterone levels increase significantly with long-term use of moclobemide in depressed males.[112]

Moclobemide also has neuroprotective properties in its demonstrated anti-hypoxia or anti-ischemia effects; there is a possibility that moclobemide may possess similar neuro-rescuing properties, similar to selegiline, however, research is required to determine this.[9] Moclobemide has also been demonstrated in a single dose research study to possess antinociceptive properties.[113]

Platelet MAO is of the MAO-B and this is inhibited only to a small degree in humans; the inhibition is due to low levels of metabolites of moclobemide that have MAO-B inhibiting properties.[114] Moclobemide has been reported to be a mixed MAO-A/MAO-B inhibitor in rats but in man, it has been reported to be a pure MAO-A inhibitor,[115] blocking the decomposition of norepinephrine, serotonin and, to a lesser extent, dopamine. No reuptake inhibition of any of the neurotransmitters occurs. The pharmacodynamic action encompasses activation, elevation of mood, and improvement of symptoms like dysphoria, fatigue, and difficulties in concentration. The duration and quality of sleep may be improved. In the treatment of depression the antidepressant effect often becomes evident in the first week of therapy (earlier than typically noted with TCAs/SSRIs).

MAO activity returns completely back to normal after 24 hours of the last dose, which allows for a quick switch to another antidepressant after the 24 hours.[9]

Pharmacokinetics

[edit]

In humans moclobemide is rapidly and almost completely absorbed and totally metabolised via the liver.[116] Peak plasma levels occur 0.3 to 2 hours after oral administration. The bioavailability increases during the first week of therapy from 60% to 80% and more. The elimination half-life is around 2 hours.[9][117] It is moderately bound to plasma proteins, especially albumin.[9] However, the short disposition half life somewhat increases after repeated dosing; moclobemide has an intermediate elimination half life for systemic clearance and an intermediate volume of distribution.[116] Despite its short half-life the pharmacodynamic action of a single dose persists for approximately 16 hours. The drug is almost completely metabolized in the liver; it is a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6 and CYP1A2.[118] Less than 1 percent of the drug is excreted unchanged; 92 percent of the metabolised drug is excreted within the first 12 hours.[7] The main metabolites are the N-oxide Ro 12-5637 formed via morpholine N-oxidation and lactam derivative Ro 12-8095 formed via morpholine C-oxidation;[119][120] active metabolites are found only in trace amounts. The unchanged drug (less than 1%) as well as the metabolites are excreted renally (in urine). The main degradation pathway of moclobemide is oxidation.[121] About 44 percent of the drug is lost due to the first pass effect through the liver.[122] Age and renal function do not affect the pharmacokinetics of moclobemide. However, patients with significantly reduced liver function require dose reductions due to the significant slowing of metabolism of moclobemide.[123] Food slows the absorption but does not affect the bioavailability of moclobemide.[9]

Steady state concentrations are established after one week.[116] It has been suggested that changes in dose should not be made with a gap of less than a week.[5] Moclobemide has good penetration across the blood brain barrier with peak plasma levels within the central nervous system occurring 2 hours after administration.[124]

Animal toxicology

[edit]
  • Acute toxicity: The oral LD50 values in mouse and rat are quite high, indicating a wide therapeutic index. LD50 for mice is 730 mg/kg and for rats 1,300 mg/kg. In dogs doses in excess of 300 mg/kg led to vomiting, salivation, ataxia, and drowsiness.
  • Chronic toxicity: In an 18-months-study in rats with 10 mg/kg no signs of chronic toxicity were noted, with 50 mg/kg and 250 mg/kg only a slight loss of weight, and with 250 mg/kg mildly elevated Alkaline phosphatase and Gamma-GT. Studies in dogs revealed no toxicity relevant for humans. No evidence for a possible hepatic or cardiovascular toxicity was found.

History

[edit]

Irreversible MAOI antidepressants were discovered accidentally in the 1950s but their popularity declined as their toxicity especially their dangerous food interactions became apparent and rival tricyclic antidepressants were discovered. Reversible MAOIs were developed in the hope that they would exert efficacy in depressive disorders but with less of the toxicity of the older irreversible compounds; moclobemide's discovery and marketing brought the renewed interest in MAOIs due to an absence of dangerous tyramine food interactions and potent antidepressant effects.[19][125] In 1992 moclobemide was launched onto the world markets.[126] Moclobemide was the first reversible MAO-A inhibitor to be widely marketed.[127] Moclobemide as well as other newer antidepressants such as the SSRIs led to changes in prescribing patterns and broadened the treatment options for the management of depressive disorders.[128]

When moclobemide was discovered in 1972 in Switzerland,[13] it was first hypothesized as being an antilipaemic or antibiotic, but the screenings were negative. The search for its antidepressant qualities, based on anticholinergic tests, also proved negative and moclobemide was then suspected of being an antipsychotic before its specific and reversible MAO-A inhibition qualities were detected. After the establishment of its lack of relevant interference with tyramine pressure response, clinical trials were launched in 1977 and further trials confirmed the broad antidepressant activity of RIMAs.[129] It was first approved in Sweden in 1989[15][16] and then the United Kingdom and Europe as the first reversible and selective inhibitor of MAO-A and is now approved in over 50 countries worldwide.[13] Subsequent research found that moclobemide is well tolerated in elderly patients[34] and far superior to tricyclic antidepressants in terms of side effects, tolerability and overdose. With regard to effectiveness in the treatment of depression, moclobemide was determined to be as effective as all major antidepressant drug classes. There is no need for dietary restrictions in contrast to people on irreversible MAOIs and apart from an important interaction with other serotonergic enhancing agents such as SSRIs and pethidine, there are few serious drug interactions and because of these benefits, moclobemide became regarded as a beneficial addition to medical 'prescribing arsenal'.[78][130] Additionally moclobemide was found, unlike most other antidepressants on the market, to actually improve all aspects of sexual function.[131] It is the only reversible MAOI in use in clinical practice.[9] The fact that moclobemide's pharmacokinetic properties are unaltered by age, that cognition is improved in the elderly, and moclobemide has low potential for food and drug interactions opened up a new avenue for the treatment of major depressive disorder.[9] Due to a lack of financial incentive, such as the costs of conducting the necessary trials to gain approval, moclobemide is unavailable in the USA pharmaceutical market.[13] In 2016 moclobemide was discontinued in Brazil for commercial reasons.[132]

Society and culture

[edit]

The Australian TGA approved moclobemide in December 2000.[14]

Brands

[edit]

It is sold under many trade names worldwide.[133]

Brand name listings

It is sold under many trade names worldwide including Apo-Moclob, Apo-Moclobemide, Auromid, Aurorix, Bei Su, Biorix, Depnil, Eutac, Hai Bei Lin, Langtian, Manerix, Mobemid, Moclamine, Moclo A, Moclobemid - 1 A Pharma, Moclobemid AL, Moclobemid HEXAL, Moclobemid ratiopharm, Moclobemida, Moclobemida Genedec, Moclobemida Teva, Moclobemide Actavis, Moclobemide Aurobindo, Moclobemide CF, Moclobemide Mylan, Moclobemide Sandoz, Moclobemide Sopharma, Moclobemide Teva, Moclobemid-neuraxpharm, Moclobemid-ratiopharm, Moclobeta, Moclod, moclodura, Moclostad, Mocrim, Moklar, Teva-Moclobemide, Tian Tai, Ya Zheng, and Zorix.[133]

See also

[edit]

References

[edit]
  1. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ^ a b c d Fitton A, Faulds D, Goa KL (April 1992). "Moclobemide. A review of its pharmacological properties and therapeutic use in depressive illness". Drugs. 43 (4): 561–596. doi:10.2165/00003495-199243040-00009. PMID 1377119. S2CID 195671164.
  3. ^ a b c Freeman H (December 1993). "Moclobemide". Lancet. 342 (8886–8887): 1528–1532. doi:10.1016/S0140-6736(05)80090-X. PMID 7902906. S2CID 208793357.
  4. ^ a b Schoerlin MP, Mayersohn M, Korn A, Eggers H (October 1987). "Disposition kinetics of moclobemide, a monoamine oxidase-A enzyme inhibitor: single and multiple dosing in normal subjects". Clinical Pharmacology and Therapeutics. 42 (4): 395–404. doi:10.1038/clpt.1987.169. PMID 3665338. S2CID 46130982.
  5. ^ a b c Guentert TW, Tucker G, Korn A, Pfefen JP, Haefelfinger P, Schoerlin MP (1990). "Pharmacokinetics of moclobemide after single and multiple oral dosing with 150 milligrams 3 times daily for 15 days". Acta Psychiatrica Scandinavica. Supplementum. 360: 91–93. doi:10.1111/j.1600-0447.1990.tb05345.x. PMID 2248087. S2CID 8623387.
  6. ^ Gex-Fabry M, Balant-Gorgia AE, Balant LP (February 1995). "Potential of concentration monitoring data for a short half-life drug: analysis of pharmacokinetic variability for moclobemide". Therapeutic Drug Monitoring. 17 (1): 39–46. doi:10.1097/00007691-199502000-00007. PMID 7725375. S2CID 7044652.
  7. ^ a b Jauch R, Griesser E, Oesterhelt G, Arnold W, Meister W, Ziegler WH, et al. (1990). "Biotransformation of moclobemide in humans". Acta Psychiatrica Scandinavica. Supplementum. 360: 87–90. doi:10.1111/j.1600-0447.1990.tb05344.x. PMID 2248086. S2CID 41595227.
  8. ^ Scheen AJ (May 1994). "[Drug of the month. Moclobemide (Aurorix)]". Revue Médicale de Liège (in French). 49 (5): 291–292. PMID 8023056.
  9. ^ a b c d e f g h i j k l m n o p q r s t u v w x y Nair NP, Ahmed SK, Kin NM (November 1993). "Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: focus on moclobemide". Journal of Psychiatry & Neuroscience. 18 (5): 214–225. PMC 1188542. PMID 7905288.
  10. ^ a b c d e f g h Fulton B, Benfield P (September 1996). "Moclobemide. An update of its pharmacological properties and therapeutic use". Drugs. 52 (3): 450–474. doi:10.2165/00003495-199652030-00013. PMID 8875133. S2CID 195672909.
  11. ^ a b c d e f Rossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  12. ^ a b c d Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
  13. ^ a b c d e f g h Lotufo-Neto F, Trivedi M, Thase ME (March 1999). "Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression". Neuropsychopharmacology. 20 (3): 226–247. doi:10.1016/S0893-133X(98)00075-X. PMID 10063483. S2CID 13181486.
  14. ^ a b c "PRODUCT INFORMATION MOCLOBEMIDE SANDOZ® 150mg and 300mg TABLETS". TGA eBusiness Services. Sandoz. 6 March 2012. Retrieved 16 October 2013.
  15. ^ a b Bonnet U (2002). "Moclobemide: evolution, pharmacodynamic, and pharmacokinetic properties". CNS Drug Rev. 8 (3): 283–308. doi:10.1111/j.1527-3458.2002.tb00229.x. PMC 6741699. PMID 12353059.
  16. ^ a b Semple D, Smyth R (2013). Oxford Handbook of Psychiatry. Oxford Medical Handbooks. OUP Oxford. p. 29. ISBN 978-0-19-969388-7. Retrieved 10 October 2024.
  17. ^ a b c Kennedy SH (March 1997). "Continuation and maintenance treatments in major depression: the neglected role of monoamine oxidase inhibitors". Journal of Psychiatry & Neuroscience. 22 (2): 127–131. PMC 1188835. PMID 9074307.
  18. ^ Cesura AM, Pletscher A (1992). "The new generation of monoamine oxidase inhibitors". Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques. Vol. 38. pp. 171–297. doi:10.1007/978-3-0348-7141-9_3. ISBN 978-3-0348-7143-3. PMID 1609114.
  19. ^ a b Roth M, Guelfi JD (September 1992). "The efficacy of reversible monoamine oxidase inhibitors in depressive illness". Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie. 37 (Suppl 1): 18–24. PMID 1394027.
  20. ^ Amrein R, Hetzel W, Stabl M, Schmid-Burgk W (January 1993). "RIMA--a new concept in the treatment of depression with moclobemide". International Clinical Psychopharmacology. 7 (3–4): 123–132. doi:10.1097/00004850-199300730-00001. PMID 8468432. S2CID 41433853.
  21. ^ Mitchell PB, Mitchell MS (September 1994). "The management of depression. Part 2. The place of the new antidepressants". Australian Family Physician. 23 (9): 1771–3, 1776–81. PMID 7980178.
  22. ^ Lecrubier Y, Guelfi JD (1990). "Efficacy of reversible inhibitors of monoamine oxidase-A in various forms of depression". Acta Psychiatrica Scandinavica. Supplementum. 360: 18–23. doi:10.1111/j.1600-0447.1990.tb05319.x. PMID 2248063. S2CID 25480681.
  23. ^ a b Priest RG, Baldwin DS, Bullock T, Kibel D, Smeyatsky N, Steinert J (June 1992). "Recent advances in antidepressant drugs". South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde. 1992 (Suppl): 1–4. PMID 1609337.
  24. ^ Angst J, Amrein R, Stabl M (August 1995). "Moclobemide and tricyclic antidepressants in severe depression: meta-analysis and prospective studies". Journal of Clinical Psychopharmacology. 15 (4 Suppl 2): 16S–23S. doi:10.1097/00004714-199508001-00004. PMID 7593725.
  25. ^ a b c d Priest RG, Gimbrett R, Roberts M, Steinert J (1995). "Reversible and selective inhibitors of monoamine oxidase A in mental and other disorders". Acta Psychiatrica Scandinavica. Supplementum. 386: 40–43. doi:10.1111/j.1600-0447.1995.tb05923.x. PMID 7717094. S2CID 25115362.
  26. ^ Spoov J, Suominen JY, Lahdelma RL, Katila H, Kymäläinen O, Isometsä E, et al. (February 1993). "Do reversed depressive symptoms occur together as a syndrome?". Journal of Affective Disorders. 27 (2): 131–134. doi:10.1016/0165-0327(93)90086-Y. PMID 8440808.
  27. ^ Angst J, Scheidegger P, Stabl M (1993). "Efficacy of moclobemide in different patient groups. Results of new subscales of the Hamilton Depression Rating Scale". Clinical Neuropharmacology. 16 (Suppl 2): S55–S62. PMID 8313398.
  28. ^ Woggon B (January 1993). "The role of moclobemide in endogenous depression: a survey of recent data". International Clinical Psychopharmacology. 7 (3–4): 137–139. doi:10.1097/00004850-199300730-00003. PMID 8468434. S2CID 25765092.
  29. ^ Silverstone T (January 1993). "Moclobemide--placebo-controlled trials". International Clinical Psychopharmacology. 7 (3–4): 133–136. doi:10.1097/00004850-199300730-00002. PMID 8468433. S2CID 30905866.
  30. ^ Philipp M, Kohnen R, Benkert O (January 1993). "A comparison study of moclobemide and doxepin in major depression with special reference to effects on sexual dysfunction". International Clinical Psychopharmacology. 7 (3–4): 149–153. doi:10.1097/00004850-199300730-00005. PMID 8468436. S2CID 19429752.
  31. ^ Tikal K, Hrabánková M (June 1993). "[Indications for antidepressive agents in relation to diseases of the cardiovascular system]". Ceskoslovenska Psychiatrie (in Czech). 89 (3): 163–165. PMID 8353831.
  32. ^ Delini-Stula A, Mikkelsen H, Angst J (October 1995). "Therapeutic efficacy of antidepressants in agitated anxious depression--a meta-analysis of moclobemide studies". Journal of Affective Disorders. 35 (1–2): 21–30. doi:10.1016/0165-0327(95)00034-K. PMID 8557884.
  33. ^ Stabl M, Biziére K, Schmid-Burgk W, Amrein R (1989). "Review of comparative clinical trials. Moclobemide vs tricyclic antidepressants and vs placebo in depressive states". Journal of Neural Transmission. Supplementum. 28: 77–89. PMID 2677244.
  34. ^ a b Amrein R, Stabl M, Henauer S, Affolter E, Jonkanski I (December 1997). "Efficacy and tolerability of moclobemide in comparison with placebo, tricyclic antidepressants, and selective serotonin reuptake inhibitors in elderly depressed patients: a clinical overview". Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie. 42 (10): 1043–1050. doi:10.1177/070674379704201005. PMID 9469236. S2CID 18651277.
  35. ^ Versiani M, Nardi AE, Figueira I (July 1998). "Pharmacotherapy of dysthymia: review and new findings". European Psychiatry. 13 (4): 203–209. doi:10.1016/S0924-9338(98)80005-9. PMID 19698626. S2CID 7786359.
  36. ^ Nutt D, Montgomery SA (June 1996). "Moclobemide in the treatment of social phobia". International Clinical Psychopharmacology. 11 (3): 77–82. doi:10.1097/00004850-199606000-00013. PMID 8923114. S2CID 2463856.
  37. ^ Blanco C, Bragdon LB, Schneier FR, Liebowitz MR (February 2013). "The evidence-based pharmacotherapy of social anxiety disorder". The International Journal of Neuropsychopharmacology. 16 (1): 235–249. doi:10.1017/S1461145712000119. PMID 22436306.
  38. ^ Versiani M, Nardi AE, Mundim FD, Alves AB, Liebowitz MR, Amrein R (September 1992). "Pharmacotherapy of social phobia. A controlled study with moclobemide and phenelzine". The British Journal of Psychiatry. 161 (3): 353–360. doi:10.1192/bjp.161.3.353. PMID 1393304. S2CID 45341667.
  39. ^ Versiani M, Amrein R, Montgomery SA (September 1997). "Social phobia: long-term treatment outcome and prediction of response--a moclobemide study". International Clinical Psychopharmacology. 12 (5): 239–254. doi:10.1097/00004850-199709000-00001. PMID 9466158. S2CID 7144850.
  40. ^ Bonnet U (2003). "Moclobemide: therapeutic use and clinical studies". CNS Drug Reviews. 9 (1): 97–140. doi:10.1111/j.1527-3458.2003.tb00245.x. PMC 6741704. PMID 12595913.
  41. ^ a b Berlin I, Saïd S, Spreux-Varoquaux O, Launay JM, Olivares R, Millet V, et al. (October 1995). "A reversible monoamine oxidase A inhibitor (moclobemide) facilitates smoking cessation and abstinence in heavy, dependent smokers". Clinical Pharmacology and Therapeutics. 58 (4): 444–452. doi:10.1016/0009-9236(95)90058-6. PMID 7586937. S2CID 25252395.
  42. ^ Hajizadeh A, Howes S, Theodoulou A, Klemperer E, Hartmann-Boyce J, Livingstone-Banks J, et al. (May 2023). "Antidepressants for smoking cessation". The Cochrane Database of Systematic Reviews. 2023 (5): CD000031. doi:10.1002/14651858.CD000031.pub6. PMC 10207863. PMID 37230961.
  43. ^ Tiller JW, Bouwer C, Behnke K (October 1997). "Moclobemide for anxiety disorders: a focus on moclobemide for panic disorder". International Clinical Psychopharmacology. 12 (Suppl 6): S27–S30. doi:10.1097/00004850-199710006-00006. PMID 9466172. S2CID 23852733.
  44. ^ Heymann RE, Paiva E, Helfenstein M, Pollak DF, Martinez JE, Provenza JR, et al. (2010). "Brazilian consensus on the treatment of fibromyalgia". Revista Brasileira de Reumatologia. 50 (1): 56–66. doi:10.1590/S0482-50042010000100006. PMID 21125141.
  45. ^ Liebowitz MR, Hollander E, Schneier F, Campeas R, Welkowitz L, Hatterer J, et al. (1990). "Reversible and irreversible monoamine oxidase inhibitors in other psychiatric disorders". Acta Psychiatrica Scandinavica. Supplementum. 360: 29–34. doi:10.1111/j.1600-0447.1990.tb05321.x. PMID 2248064. S2CID 30319319.
  46. ^ Menkes DB, Thomas MC, Phipps RF (September 1994). "Moclobemide for menopausal flushing". Lancet. 344 (8923): 691–692. doi:10.1016/S0140-6736(94)92131-8. PMID 7915384. S2CID 43226134.
  47. ^ Baumann P (December 1996). "Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors". Clinical Pharmacokinetics. 31 (6): 444–469. doi:10.2165/00003088-199631060-00004. PMID 8968657. S2CID 31923953.
  48. ^ Hill S, Yau K, Whitwam J (1992). "MAOIs to RIMAs in anaesthesia--a literature review". Psychopharmacology. 106 (Suppl): S43–S45. doi:10.1007/bf02246234. PMID 1546140. S2CID 11555131.
  49. ^ Blom-Peters L, Lamy M (1993). "Monoamine oxidase inhibitors and anesthesia: an updated literature review". Acta Anaesthesiologica Belgica. 44 (2): 57–60. PMID 8237297.
  50. ^ Alevizos B, Hatzimanolis J, Markianos M, Stefanis CN (April 1993). "Clinical, endocrine and neurochemical effects of moclobemide in depressed patients". Acta Psychiatrica Scandinavica. 87 (4): 285–290. doi:10.1111/j.1600-0447.1993.tb03373.x. PMID 8488751. S2CID 7859228.
  51. ^ Chan-Palay V (1992). "Depression and senile dementia of the Alzheimer type: a role for moclobemide". Psychopharmacology. 106 (Suppl): S137–S139. doi:10.1007/bf02246259. PMID 1546130. S2CID 22599717.
  52. ^ De Vanna M, Kummer J, Agnoli A, Gentili P, Lorizio A, Anand R (1990). "Moclobemide compared with second-generation antidepressants in elderly people". Acta Psychiatrica Scandinavica. Supplementum. 360: 64–66. doi:10.1111/j.1600-0447.1990.tb05335.x. PMID 2248077. S2CID 25514792.
  53. ^ Tiller JW (1992). "Post-stroke depression". Psychopharmacology. 106 (Suppl): S130–S133. doi:10.1007/bf02246257. PMID 1546128. S2CID 7694939.
  54. ^ Wesnes K, Anand R, Lorscheid T (1990). "Potential of moclobemide to improve cerebral insufficiency identified using a scopolamine model of aging and dementia". Acta Psychiatrica Scandinavica. Supplementum. 360: 71–72. doi:10.1111/j.1600-0447.1990.tb05338.x. PMID 2248080. S2CID 43677453.
  55. ^ Guentert TW, Banken L, Hilton S, Holford NH (August 1995). "Moclobemide: relationships between dose, drug concentration in plasma, and occurrence of adverse events". Journal of Clinical Psychopharmacology. 15 (4 Suppl 2): 84S–94S. doi:10.1097/00004714-199508001-00014. PMID 7593736.
  56. ^ Swinkels JA, de Jonghe F (January 1995). "Safety of antidepressants". International Clinical Psychopharmacology. 9 (Suppl 4): 19–25. doi:10.1097/00004850-199501004-00003. PMID 7622819. S2CID 37450365.
  57. ^ Moll E, Neumann N, Schmid-Burgk W, Stabl M, Amrein R (1994). "Safety and efficacy during long-term treatment with moclobemide". Clinical Neuropharmacology. 17 (Suppl 1): S74–S87. doi:10.1097/00002826-199417001-00009. PMID 7954486. S2CID 33885246.
  58. ^ a b Versiani M, Nardi AE, Figueira IL, Stabl M (1990). "Tolerability of moclobemide, a new reversible inhibitor of monoamine oxidase-A, compared with other antidepressants and placebo". Acta Psychiatrica Scandinavica. Supplementum. 360: 24–28. doi:10.1111/j.1600-0447.1990.tb05320.x. PMID 2123366. S2CID 46436750.
  59. ^ Amrein R, Hetzel W, Stabl M, Schmid-Burgk W (September 1992). "RIMA: a safe concept in the treatment of depression with moclobemide". Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie. 37 (Suppl 1): 7–11. PMID 1394030.
  60. ^ a b c Norman TR, Burrows GD (January 1995). "A risk-benefit assessment of moclobemide in the treatment of depressive disorders". Drug Safety. 12 (1): 46–54. doi:10.2165/00002018-199512010-00004. PMID 7741983. S2CID 37305194.
  61. ^ a b Tiller JW (1990). "Antidepressants, alcohol and psychomotor performance". Acta Psychiatrica Scandinavica. Supplementum. 360: 13–17. doi:10.1111/j.1600-0447.1990.tb05318.x. PMID 2248062. S2CID 40365188.
  62. ^ Hindmarch I, Kerr J (1992). "Behavioural toxicity of antidepressants with particular reference to moclobemide". Psychopharmacology. 106 (Suppl): S49–S55. doi:10.1007/bf02246236. PMID 1546141. S2CID 27815494.
  63. ^ Alderman CP, Callary JA, Kent AL (July 1992). "Peripheral oedema associated with moclobemide". The Medical Journal of Australia. 157 (2): 144. doi:10.5694/j.1326-5377.1992.tb137069.x. PMID 1630391.
  64. ^ Tiller JW, Johnson GF, Burrows GD (August 1995). "Moclobemide for depression: an Australian psychiatric practice study". Journal of Clinical Psychopharmacology. 15 (4 Suppl 2): 31S–34S. doi:10.1097/00004714-199508001-00006. PMID 7593727.
  65. ^ Rimón R, Jääskeläinen J, Kaartinen P, Kalli A, Kilponen E, Koskinen T, et al. (January 1993). "Moclobemide versus imipramine in depressed out-patients: a double-blind multi-centre study". International Clinical Psychopharmacology. 7 (3–4): 141–147. doi:10.1097/00004850-199300730-00004. PMID 8468435. S2CID 41323843.
  66. ^ "Moclobemide: a reversible MAO-A-inhibitor showing weaker antidepressant effect than clomipramine in a controlled multicenter study. Danish University Antidepressant Group". Journal of Affective Disorders. 28 (2): 105–116. June 1993. doi:10.1016/0165-0327(93)90039-M. PMID 8354766.
  67. ^ Gram LF (September 1994). "[Antidepressive drug therapy, suicidal tendency and suicide, 2 cases reported in connection with moclobemide (Aurorix) therapy]". Ugeskrift for Laeger (in Danish). 156 (38): 5542. PMID 7941097.
  68. ^ Isacsson G, Holmgren P, Druid H, Bergman U (August 1997). "The utilization of antidepressants--a key issue in the prevention of suicide: an analysis of 5281 suicides in Sweden during the period 1992-1994". Acta Psychiatrica Scandinavica. 96 (2): 94–100. doi:10.1111/j.1600-0447.1997.tb09912.x. PMID 9272192. S2CID 32663665.
  69. ^ Curran S, de Pauw K (February 1998). "Selecting an antidepressant for use in a patient with epilepsy. Safety considerations". Drug Safety. 18 (2): 125–133. doi:10.2165/00002018-199818020-00004. PMID 9512919. S2CID 32592676.
  70. ^ Bisserbe JC, Lépine JP (1994). "Moclobemide in social phobia: a pilot open study. GRP Group. Groupe de Recherche en Psychopharmacologie". Clinical Neuropharmacology. 17 (Suppl 1): S88–S94. doi:10.1097/00002826-199417001-00010. PMID 7954487. S2CID 27531475.
  71. ^ "NAME OF THE DRUG AURORIX". TGA eBusiness Services. Meda Valeant Pharma Australia Pty Limited. 7 January 2013. Retrieved 16 October 2013.
  72. ^ a b Zimmer R, Gieschke R, Fischbach R, Gasic S (1990). "Interaction studies with moclobemide". Acta Psychiatrica Scandinavica. Supplementum. 360: 84–86. doi:10.1111/j.1600-0447.1990.tb05343.x. PMID 2248085. S2CID 46550463.
  73. ^ Amrein R, Güntert TW, Dingemanse J, Lorscheid T, Stabl M, Schmid-Burgk W (1992). "Interactions of moclobemide with concomitantly administered medication: evidence from pharmacological and clinical studies". Psychopharmacology. 106 (Suppl): S24–S31. doi:10.1007/bf02246229. PMID 1546135. S2CID 10570722.
  74. ^ Dingemanse J (January 1993). "An update of recent moclobemide interaction data". International Clinical Psychopharmacology. 7 (3–4): 167–180. doi:10.1097/00004850-199300730-00008. PMID 8468439. S2CID 11427093.
  75. ^ Duncan D, Sayal K, McConnell H, Taylor D (March 1998). "Antidepressant interactions with warfarin". International Clinical Psychopharmacology. 13 (2): 87–94. doi:10.1097/00004850-199803000-00006. PMID 9669190. S2CID 39487146.
  76. ^ Livingston MG, Livingston HM (April 1996). "Monoamine oxidase inhibitors. An update on drug interactions". Drug Safety. 14 (4): 219–227. doi:10.2165/00002018-199614040-00002. PMID 8713690. S2CID 46742172.
  77. ^ Hilton SE, Maradit H, Möller HJ (1997). "Serotonin syndrome and drug combinations: focus on MAOI and RIMA". European Archives of Psychiatry and Clinical Neuroscience. 247 (3): 113–119. doi:10.1007/BF03033064. PMID 9224903. S2CID 25320878.
  78. ^ a b Tiller JW (September 1993). "Clinical overview on moclobemide". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 17 (5): 703–712. doi:10.1016/0278-5846(93)90054-V. PMID 8255982. S2CID 8473676.
  79. ^ Zivanović O, Till E (1992). "[Serotonin syndrome--a case account]". Medicinski Pregled. 45 (3–4): 116–118. PMID 16104086.
  80. ^ Spigset O, Mjörndal T, Lövheim O (January 1993). "Serotonin syndrome caused by a moclobemide-clomipramine interaction". BMJ. 306 (6872): 248. doi:10.1136/bmj.306.6872.248. PMC 1676747. PMID 8443525.
  81. ^ Roxanas MG, Machado JF (May 1998). "Serotonin syndrome in combined moclobemide and venlafaxine ingestion". The Medical Journal of Australia. 168 (10): 523–524. doi:10.5694/j.1326-5377.1998.tb141428.x. PMID 9631680.
  82. ^ König F, Wolfersdorf M, Löble M, Wössner S, Hauger B (July 1997). "Trimipramine and maprotiline plasma levels during combined treatment with moclobemide in therapy-resistant depression". Pharmacopsychiatry. 30 (4): 125–127. doi:10.1055/s-2007-979497. PMID 9271778. S2CID 35570626.
  83. ^ Rolan P (October 1997). "Potential drug interactions with the novel antimigraine compound zolmitriptan (Zomig, 311C90)". Cephalalgia. 17 (18_suppl): 21–27. doi:10.1177/0333102497017S1804. PMID 9399014. S2CID 30479192.
  84. ^ Härtter S, Dingemanse J, Baier D, Ziegler G, Hiemke C (January 1998). "Inhibition of dextromethorphan metabolism by moclobemide". Psychopharmacology. 135 (1): 22–26. doi:10.1007/s002130050481. PMID 9489930. S2CID 19450106.
  85. ^ "Moclobemide". go.drugbank.com. DrugBank online. Retrieved 7 March 2021. Accession Number DB01171
  86. ^ Lavian G, Finberg JP, Youdim MB (1993). "The advent of a new generation of monoamine oxidase inhibitor antidepressants: pharmacologic studies with moclobemide and brofaromine". Clinical Neuropharmacology. 16 (Suppl 2): S1–S7. PMID 8313392.
  87. ^ Da Prada M, Zürcher G, Wüthrich I, Haefely WE (1988). "On tyramine, food, beverages and the reversible MAO inhibitor moclobemide". Journal of Neural Transmission. Supplementum. 26: 31–56. PMID 3283290.
  88. ^ Zimmer R (1990). "Relationship between tyramine potentiation and monoamine oxidase (MAO) inhibition: comparison between moclobemide and other MAO inhibitors". Acta Psychiatrica Scandinavica. Supplementum. 360: 81–83. doi:10.1111/j.1600-0447.1990.tb05342.x. PMID 2248084. S2CID 9041656.
  89. ^ Heinonen EH, Myllylä V (July 1998). "Safety of selegiline (deprenyl) in the treatment of Parkinson's disease". Drug Safety. 19 (1): 11–22. doi:10.2165/00002018-199819010-00002. PMID 9673855. S2CID 9632549.
  90. ^ Korn A, Wagner B, Moritz E, Dingemanse J (1996). "Tyramine pressor sensitivity in healthy subjects during combined treatment with moclobemide and selegiline". European Journal of Clinical Pharmacology. 49 (4): 273–278. doi:10.1007/BF00226327. PMID 8857072. S2CID 39823545.
  91. ^ Dingemanse J, Hussain Y, Korn A (April 1996). "Tyramine pharmacodynamics during combined administration of lazabemide and moclobemide". International Journal of Clinical Pharmacology and Therapeutics. 34 (4): 172–177. PMID 8861736.
  92. ^ Hetzel W (1992). "Safety of moclobemide taken in overdose for attempted suicide". Psychopharmacology. 106 (Suppl): S127–S129. doi:10.1007/bf02246256. PMID 1546127. S2CID 26798620.
  93. ^ Myrenfors PG, Eriksson T, Sandsted CS, Sjöberg G (February 1993). "Moclobemide overdose". Journal of Internal Medicine. 233 (2): 113–115. doi:10.1111/j.1365-2796.1993.tb00662.x. PMID 8433071. S2CID 221919828.
  94. ^ Neuvonen PJ, Pohjola-Sintonen S, Tacke U, Vuori E (December 1993). "Five fatal cases of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses". Lancet. 342 (8884): 1419. doi:10.1016/0140-6736(93)92774-N. PMID 7901695. S2CID 39514927.
  95. ^ Isacsson G, Redfors I, Wasserman D, Bergman U (December 1994). "Choice of antidepressants: questionnaire survey of psychiatrists and general practitioners in two areas of Sweden". BMJ. 309 (6968): 1546–1549. doi:10.1136/bmj.309.6968.1546. PMC 2541721. PMID 7819894.
  96. ^ Curtin F, Berney P, Kaufmann C (September 2002). "Moclobemide discontinuation syndrome predominantly presenting with influenza-like symptoms". Journal of Psychopharmacology. 16 (3): 271–272. doi:10.1177/026988110201600314. PMID 12236637. S2CID 23038043.
  97. ^ Coupland NJ, Bell CJ, Potokar JP (October 1996). "Serotonin reuptake inhibitor withdrawal". Journal of Clinical Psychopharmacology. 16 (5): 356–362. doi:10.1097/00004714-199610000-00003. PMID 8889907.
  98. ^ Ghanbarpour A, Hadizadeh F, Piri F, Rashidi-Ranjbar P (April 1997). "Synthesis, conformational analysis and antidepressant activity of moclobemide new analogues". Pharmaceutica Acta Helvetiae. 72 (2): 119–122. doi:10.1016/S0031-6865(97)00004-6. PMID 9112832.
  99. ^ a b Haefely W, Burkard WP, Cesura AM, Kettler R, Lorez HP, Martin JR, et al. (1992). "Biochemistry and pharmacology of moclobemide, a prototype RIMA". Psychopharmacology. 106 (Suppl): S6-14. doi:10.1007/bf02246225. PMID 1546143. S2CID 23563947.
  100. ^ "Manerix Product Monograph" (PDF). Valeant Canada LP. Retrieved 30 June 2022.
  101. ^ Sacher J, Houle S, Parkes J, Rusjan P, Sagrati S, Wilson AA, et al. (November 2011). "Monoamine oxidase A inhibitor occupancy during treatment of major depressive episodes with moclobemide or St. John's wort: an [11C]-harmine PET study". Journal of Psychiatry & Neuroscience. 36 (6): 375–82. doi:10.1503/jpn.100117. PMC 3201991. PMID 21463543.
  102. ^ Chiuccariello L, Cooke RG, Miler L, Levitan RD, Baker GB, Kish SJ, et al. (August 2015). "Monoamine Oxidase-A Occupancy by Moclobemide and Phenelzine: Implications for the Development of Monoamine Oxidase Inhibitors". The International Journal of Neuropsychopharmacology. 19 (1): pyv078. doi:10.1093/ijnp/pyv078. PMC 4772270. PMID 26316187.
  103. ^ Lotufo-Neto F, Trivedi M, Thase ME (March 1999). "Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression". Neuropsychopharmacology. 20 (3): 226–247. doi:10.1016/S0893-133X(98)00075-X. PMID 10063483. S2CID 13181486.
  104. ^ Cho HU, Kim S, Sim J, Yang S, An H, Nam MH, et al. (July 2021). "Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis". Experimental & Molecular Medicine. 53 (7): 1148–1158. doi:10.1038/s12276-021-00646-3. PMC 8333267. PMID 34244591. S2CID 235786369.
  105. ^ Radat F, Berlin I, Spreux-Varoquaux O, Elatki S, Ferreri M, Puech AJ (October 1996). "Initial monoamine oxidase-A inhibition by moclobemide does not predict the therapeutic response in patients with major depression. A double blind, randomized study". Psychopharmacology. 127 (4): 370–376. doi:10.1007/bf02806017. PMID 8923574. S2CID 52872435.
  106. ^ Holford NH, Guentert TW, Dingemanse J, Banken L (May 1994). "Monoamine oxidase-A: pharmacodynamics in humans of moclobemide, a reversible and selective inhibitor". British Journal of Clinical Pharmacology. 37 (5): 433–439. doi:10.1111/j.1365-2125.1994.tb05710.x. PMC 1364898. PMID 7519866.
  107. ^ Dingemanse J, Berlin I, Payan C, Thiede HM, Puech AJ (1992). "Comparative investigation of the effect of moclobemide and toloxatone on monoamine oxidase activity and psychometric performance in healthy subjects". Psychopharmacology. 106 (Suppl): S68–S70. doi:10.1007/bf02246239. PMID 1546145. S2CID 22329953.
  108. ^ Haefely W, Burkard WP, Cesura A, Colzi A, Kettler R, Lorez HP, et al. (1993). "Pharmacology of moclobemide". Clinical Neuropharmacology. 16 (Suppl 2): S8-18. PMID 8313402.
  109. ^ Lin A, Song C, Kenis G, Bosmans E, De Jongh R, Scharpé S, et al. (April 2000). "The in vitro immunosuppressive effects of moclobemide in healthy volunteers". Journal of Affective Disorders. 58 (1): 69–74. doi:10.1016/S0165-0327(99)00076-2. PMID 10760560.
  110. ^ Mori S, Zanardi R, Popoli M, Garbini S, Brunello N, Smeraldi E, et al. (1998). "cAMP-dependent phosphorylation system after short and long-term administration of moclobemide". Journal of Psychiatric Research. 32 (2): 111–115. doi:10.1016/S0022-3956(98)00003-X. PMID 9694007.
  111. ^ Da Prada M, Kettler R, Keller HH, Burkard WP, Haefely WE (1989). "Preclinical profiles of the novel reversible MAO-A inhibitors, moclobemide and brofaromine, in comparison with irreversible MAO inhibitors". Journal of Neural Transmission. Supplementum. 28: 5–20. PMID 2677242.
  112. ^ Markianos M, Alevizos V, Stefanis C (1991). "Plasma sex hormones and urinary biogenic amine metabolites during treatment of male depressed patients with the monoamine oxidase inhibitor moclobemide". Neuro Endocrinology Letters. 13 (1): 49–55. ISSN 0172-780X.
  113. ^ Coquoz D, Porchet HC, Dayer P (September 1993). "Central analgesic effects of desipramine, fluvoxamine, and moclobemide after single oral dosing: a study in healthy volunteers". Clinical Pharmacology and Therapeutics. 54 (3): 339–344. doi:10.1038/clpt.1993.156. PMID 8375130. S2CID 8229797.
  114. ^ Bitsios P, Langley RW, Tavernor S, Pyykkö K, Scheinin M, Szabadi E, et al. (June 1998). "Comparison of the effects of moclobemide and selegiline on tyramine-evoked mydriasis in man". British Journal of Clinical Pharmacology. 45 (6): 551–558. doi:10.1046/j.1365-2125.1998.00729.x. PMC 1873648. PMID 9663810.
  115. ^ Vallès B, Coassolo P, De Sousa G, Aubert C, Rahmani R (October 1993). "In vitro hepatic biotransformation of moclobemide (Ro 11-1163) in man and rat". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 23 (10): 1101–1111. doi:10.3109/00498259309059425. PMID 8259692.
  116. ^ a b c Mayersohn M, Guentert TW (November 1995). "Clinical pharmacokinetics of the monoamine oxidase-A inhibitor moclobemide". Clinical Pharmacokinetics. 29 (5): 292–332. doi:10.2165/00003088-199529050-00002. PMID 8582117. S2CID 25628650.
  117. ^ Leikin JB, Paloucek FP (2007). "Moclobemide". Poisoning and toxicology handbook (4th ed.). Informa Health Care. p. 1331. ISBN 978-1-4200-4479-9. Retrieved 26 May 2009.
  118. ^ Gram LF, Guentert TW, Grange S, Vistisen K, Brøsen K (June 1995). "Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2: a panel study". Clinical Pharmacology and Therapeutics. 57 (6): 670–677. doi:10.1016/0009-9236(95)90230-9. PMID 7781267. S2CID 24783014.
  119. ^ Härtter S, Dingemanse J, Baier D, Ziegler G, Hiemke C (August 1996). "The role of cytochrome P450 2D6 in the metabolism of moclobemide". European Neuropsychopharmacology. 6 (3): 225–230. doi:10.1016/0924-977X(96)00023-5. PMID 8880082. S2CID 34201446.
  120. ^ Gram LF, Brøsen K (June 1993). "Moclobemide treatment causes a substantial rise in the sparteine metabolic ratio. Danish University Antidepressant Group". British Journal of Clinical Pharmacology. 35 (6): 649–652. doi:10.1111/j.1365-2125.1993.tb04196.x. PMC 1381610. PMID 8329293.
  121. ^ Schoerlin MP, Guentert TW (August 1989). "[Pharmacokinetics and metabolism of reversible MAO-A inhibitors in the human]". Psychiatrische Praxis (in German). 16 (Suppl 1): 11–17. PMID 2685852.
  122. ^ Raaflaub J, Haefelfinger P, Trautmann KH (1984). "Single-dose pharmacokinetics of the MAO-inhibitor moclobemide in man". Arzneimittel-Forschung. 34 (1): 80–82. PMID 6538424.
  123. ^ Goldberg RJ (August 1997). "Antidepressant use in the elderly. Current status of nefazodone, venlafaxine and moclobemide". Drugs & Aging. 11 (2): 119–131. doi:10.2165/00002512-199711020-00004. PMID 9259175. S2CID 24440475.
  124. ^ Berlin I, Zimmer R, Thiede HM, Payan C, Hergueta T, Robin L, et al. (December 1990). "Comparison of the monoamine oxidase inhibiting properties of two reversible and selective monoamine oxidase-A inhibitors moclobemide and toloxatone, and assessment of their effect on psychometric performance in healthy subjects". British Journal of Clinical Pharmacology. 30 (6): 805–816. doi:10.1111/j.1365-2125.1990.tb05445.x. PMC 1368300. PMID 1705137.
  125. ^ Rudorfer MV (1992). "Monoamine oxidase inhibitors: reversible and irreversible". Psychopharmacology Bulletin. 28 (1): 45–57. PMID 1609042.
  126. ^ Hilton S, Jaber B, Ruch R (August 1995). "Moclobemide safety: monitoring a newly developed product in the 1990s". Journal of Clinical Psychopharmacology. 15 (4 Suppl 2): 76S–83S. doi:10.1097/00004714-199508001-00013. PMID 7593735.
  127. ^ Volz HP, Gleiter CH, Möller HJ (May 1996). "[Monoamine oxidase inhibitors in psychiatry. Status of current knowledge]". Der Nervenarzt (in German). 67 (5): 339–347. PMID 9005342.
  128. ^ Mitchell PB, Mitchell MS (August 1994). "The management of depression. The place of the new antidepressants. Part 1. General overview". Australian Family Physician. 23 (8): 1555–9, 1562. PMID 7980156.
  129. ^ Angst J, Amrein R, Stabl M (June 1996). "Moclobemide: a paradigm of research in clinical psychopharmacology". International Clinical Psychopharmacology. 11 (Suppl 3): 3–7. doi:10.1097/00004850-199606003-00002. PMID 8923103. S2CID 37604541.
  130. ^ Bech P (August 1993). "Acute therapy of depression". The Journal of Clinical Psychiatry. 54 (Suppl): 18–27, discussion 28. PMID 8253702.
  131. ^ Chebili S, Abaoub A, Mezouane B, Le Goff JF (1998). "[Antidepressants and sexual stimulation: the correlation]". L'Encephale (in French). 24 (3): 180–184. PMID 9696909.
  132. ^ "Aurorix®(moclobemida) - Meda". www.medapharma.com.br (in Brazilian Portuguese). Retrieved 2018-09-17.
  133. ^ a b "Moclobemide International Brands". Drugs.com. Retrieved 3 June 2017.

Further reading

[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=Moclobemide&oldid=1256775130"