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Amitriptyline/perphenazine

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Amitriptyline/perphenazine
Combination of
AmitriptylineTricyclic antidepressant
PerphenazineTypical antipsychotic
Clinical data
Trade namesDuo-Vil, Etrafon, Triavil, Triptafen
AHFS/Drugs.comConsumer Drug Information
License data
Routes of
administration		Oral
Legal status
Legal status
Identifiers
CAS Number
KEGG

Amitriptyline/perphenazine (Duo-Vil, Etrafon, Triavil, Triptafen) is a formulation that contains the tricyclic antidepressant amitriptyline and the medium-potency typical (first-generation) antipsychotic, perphenazine. In the United States amitriptyline/perphenazine is marketed by Mylan Pharmaceuticals Inc. and Remedy Repack Inc.[1][2]

Medical uses

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In the United States amitriptyline/perphenazine is indicated for the treatment of patients with:[1][2][3]

  • Moderate to severe anxiety and/or agitation and depression
  • Depression and anxiety in association with chronic physical disease
  • Schizophrenia with prominent depressive symptoms

Adverse effects

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Common (>1% incidence) adverse effects include
[1][2][4]
  • Blurred vision
  • Constipation
  • Dry mouth
  • Nasal congestion
  • Increased appetite
  • Weight gain
  • Nausea
  • Dizziness
  • Headache
  • Vomiting
Unknown frequency adverse effects include
[1][2][4]
  • Pigmentation of the cornea and lens
  • Hyperglycaemia
  • Hypoglycaemia
  • Disturbed concentration
  • Excitement
  • Anxiety
  • Insomnia
  • Restlessness
  • Nightmares
  • Weakness
  • Fatigue
  • Diaphoresis — excessive/abnormal sweating.
Uncommon/Rare adverse effects include
[1][2][4]
  • Tardive dyskinesia, an often irreversible adverse effect that usually results from chronic use antipsychotic medications, especially the high-potency first-generation antipsychotics. It is characterised by slow (hence tardive), involuntary, repetitive, purposeless muscle movements.
  • Neuroleptic malignant syndrome, a potentially fatal complication of antipsychotic drug use. It is characterised by the following symptoms:
  • Muscle rigidity
  • Tremors
  • Mental status change (e.g., hallucinations, agitation, stupor, confusion, etc.)
  • Hyperthermia
  • Autonomic instability (e.g., tachycardia, high blood pressure, diaphoresis, diarrhoea, etc.)

Pharmacology

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See also: Amitriptyline § Pharmacology, and Perphenazine § Pharmacology

Binding affinities (Ki [nM]; for human cloned receptors when available)[5][6][7]

Molecular target Amitriptyline Nortriptyline (Amitriptyline's active metabolite) Perphenazine Notes
SERT 3.13 16.5 ? It is this and its NET-inhibiting action is believed to give amitriptyline its antidepressant action.
NET 22.4 4.37 ? See above.
DAT 5380 3100 ?
5-HT1A 450 294 421 Binding for human brain receptors had to be substituted in amitriptyline (AMI) and nortriptyline's (NOR) cases
5-HT2A 4.3 5 5.6 Binding for cloned rat receptors had to be substituted for AMI & NOR. Binding to this receptor is believed to be what gives the newer (atypical) antipsychotics, clozapine, quetiapine, olanzapine, ziprasidone, risperidone, sertindole and zotepine their lower extrapyramidal side effect (EPS) liability.
5-HT2C 6.15 8.5 132 (Binding) As above. This action is believed to be partly responsible for the lower EPS liability of newer antipsychotics and also responsible for their higher weight gain liability compared to most typical antipsychotics.
5-HT6 103 148 17 Cloned rat receptor was substituted for NOR's binding.
5-HT7 114 ? 23 Cloned rat receptor was substituted for AMI.
α1A 24 55 10 Human brain receptors were substituted for AMI and NOR.
α2A 690 2030 810.5 As above.
D2 1460 2570 0.16 As above.
D3 206 ? 0.13 Human receptors (their source was undefined) had to be substituted for AMI.
H1 1.1 15.1 8 This receptor is at least partly responsible for the sedating effects of these three drugs and hence this combination product. Possibly also partly responsible for their weight gain liability.
M1 12.9 40 1500 This is the main receptor responsible for the anticholinergic side effects mentioned above.
M3 25.9 50 1848 This receptor is believed to be partly responsible for the metabolic adverse effects of the atypical antipsychotics.
σ 300 2000 31.5 All three values are for binding to the guinea pig brain receptors.

See also

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References

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  1. ^ a b c d e "PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE tablet, film coated [Mylan Pharmaceuticals Inc.]". DailyMed. National Library of Medicine. Retrieved 7 October 2013.
  2. ^ a b c d e "PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE tablet [REMEDYREPACK INC. ]". DailyMed. National Library of Medicine. Retrieved 7 October 2013.
  3. ^ amitriptyline/perphenazine (Rx) - Etrafon, Triptafen, Triavil [Internet]. Medscape Reference. [cited 2013 Oct 7]. Available from: http://reference.medscape.com/drug/etrafon-triptafen-amitriptyline-perphenazine-342946
  4. ^ a b c Truven Health Analytics, Inc. DRUGDEX® System (Internet) [cited 2013 Oct 7]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  5. ^ National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Oct 7]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: "PDSP Database - UNC". Archived from the original on 2013-11-08. Retrieved 2013-12-01.
  6. ^ Brunton L, Chabner B, Knollman B (2010). Goodman and Gilman's The Pharmacological Basis of Therapeutics (Twelfth ed.). McGraw Hill Professional.
  7. ^ Taylor D, Paton C, Kapur S, Taylor D (2012). The Maudsley prescribing guidelines in psychiatry (11th ed.). Chichester, West Sussex: John Wiley & Sons.
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