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Mephentermine

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Mephentermine
Clinical data
Trade namesWyamine, Fentermin, Mephentine[1][2][3]
Other namesMephenterdrine; Mephetedrine; N-Methylphentermine; N,α,α-Trimethylphenethylamine; N,α,Dimethylampetamine; α-Methylmethamphetamine
Routes of
administration		Intravenous, intramuscular, oral, inhalation[4][5]
ATC code
Legal status
Legal status
Identifiers
  • N,2-dimethyl-1-phenylpropan-2-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.002.638 Edit this at Wikidata
Chemical and physical data
FormulaC11H17N
Molar mass163.264 g·mol−1
3D model (JSmol)
  • N(C(Cc1ccccc1)(C)C)C
  • InChI=1S/C11H17N/c1-11(2,12-3)9-10-7-5-4-6-8-10/h4-8,12H,9H2,1-3H3 checkY
  • Key:RXQCGGRTAILOIN-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Mephentermine, sold under the brand name Wyamine among others, is a sympathomimetic medication which was previously used in the treatment of low blood pressure but is mostly no longer marketed.[6][5][4][7][8] It is used by injection into a vein or muscle, by inhalation, and by mouth.[4][5]

Side effects of mephentermine include dry mouth, sedation, reflex bradycardia, arrhythmias, and hypertension.[4] Mephentermine induces the release of norepinephrine and dopamine and is described as an indirectly acting sympathomimetic and psychostimulant.[4] Its sympathomimetic effects are mediated by indirect activation of α- and β-adrenergic receptors.[5] Chemically, it is a substituted phenethylamine and amphetamine and is closely related to phentermine and methamphetamine.[4][9][1]

Mephentermine was first described and introduced for medical use by 1952.[10] It was discontinued in the United States between 2000 and 2004.[2][7] The medication appears to remain available only in India.[4][7][8] Misuse of mephentermine for recreational and performance-enhancing purposes has been increasingly encountered in modern times, especially in India.[11][4]

Medical uses

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For maintenance of blood pressure in hypotensive states, the dose for adults is 30 to 45 mg as a single dose, repeated as necessary or followed by intravenous infusion of 0.1% mephentermine in 5% dextrose, with the rate and duration of administration depending on the patient's response.[citation needed]

For hypotension secondary to spinal anesthesia in obstetric patients, the dose for adults is 15 mg as a single dose, repeated if needed. The maximum dose 30 mg.[citation needed]

Mephentermine has also been used as a decongestant.[6][5]

Available forms

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Mephentermine is available in the form of 15 and 30 mg/mL solutions for intravenous infusion or intramuscular injection and in the form of 10 mg oral tablets.[4] It has also been available in the form of inhalers.[5]

Contraindications

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Low blood pressure caused by phenothiazines, hypertension, and pheochromocytoma.[citation needed]

Patients receiving monoamine oxidase inhibitors.[citation needed]

For shock due to loss of blood or fluid, give fluid replacement therapy primarily, cardiovascular disease, hypertension, hyperthyroidism, chronic illnesses, lactation, pregnancy, skin dryness. headache.[citation needed]

Side effects

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The most common side effects of mephentermine are drowsiness, incoherence, hallucinations, convulsions, slow heart rate (reflex bradycardia). Fear, anxiety, restlessness, tremor, insomnia, confusion, irritability, and psychosis. Nausea, vomiting, reduced appetite, urinary retention, dyspnea, weakness, and neck pain.[citation needed]

Potentially fatal reactions are due to atrioventricular block, central nervous system stimulation, cerebral hemorrhage, pulmonary edema, and ventricular arrhythmias.[citation needed]

Interactions

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Mephentermine antagonizes effect of agents that lower blood pressure. Severe hypertension may occur with monoamine oxidase inhibitors and possibly tricyclic antidepressants. Additive vasoconstricting effects occur with ergot alkaloids, and oxytocin.[citation needed]

Potentially fatal drug interactions are the risk of abnormal heart rhythm in people undergoing anesthesia with cyclopropane and halothane.[citation needed]

Pharmacology

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Pharmacodynamics

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Mephentermine is thought to act as a releasing agent of norepinephrine and dopamine.[4] It is described as an indirectly acting sympathomimetic, cardiac stimulant, adrenergic, vasoconstrictor, antihypotensive agent, and psychostimulant.[1][2][8][4] Its sympathomimetic effects are mediated by indirect activation of α- and β-adrenergic receptors.[5][6]

Mephentermine appears to act by indirect stimulation of β-adrenergic receptors through causing the release of norepinephrine from its storage sites. It has a positive inotropic effect on the myocardium. AV conduction and refractory period of AV node is shortened with an increase in ventricular conduction velocity. It dilates arteries and arterioles in the skeletal muscle and mesenteric vascular beds, leading to an increase in venous return.[citation needed]

Pharmacokinetics

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Its onset of action is 5 to 15 minutes with intramuscular injection and is immediate with intravenous administration.[citation needed] Its duration of action is 4 hours with intramuscular injection and 30 minutes with intravenous administration.[citation needed]

Mephentermine, along with phentermine, is known to be produced as a metabolite of the orally administered local anesthetic oxetacaine (oxethazaine).[12][13]

Chemistry

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Mephentermine, also known as N,α,α-trimethylphenethylamine or N,α-dimethylampetamine, is a phenethylamine and amphetamine derivative.[9][1][4] It is the N-methylated analogue of phentermine (α-methylamphetamine) and is also known as N-methylphentermine.[9][1] In addition, mephentermine is the α-methylated analogue of methamphetamine or the α,α-dimethylated derivative of amphetamine.[9][4]

Synthesis

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Mephentermine can by synthesized beginning with a Henry reaction between benzaldehyde (1) and 2-nitropropane (2) to give 2-methyl-2-nitro-1-phenylpropan-1-ol (3).[14] The nitro group is reduced with zinc in sulfuric acid giving 2-phenyl-1,1-dimethylethanolamine (4). Imine formation by dehydration with benzaldehyde gives (5). Alkylation with iodomethane leads to (6). Halogenation with thionyl chloride gives (7). Lastly, a Rosenmund reduction completes the synthesis of mephentermine (8).

Synthesis of mephentermine

Mephentermine can also be synthesized by condensation of phentermine with benzaldehyde to get a Schiff base which can be alkylated with methyl iodide to give mephentermine.[15]

History

[edit]

Mephentermine was first described in the literature and was introduced for medical use under the brand name Wyamine by 1952.[10] It was discontinued in the United States between 2000 and 2004.[2][7]

Society and culture

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Names

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Mephentermine is the generic name of the drug and its INNTooltip International Nonproprietary Name, BANTooltip British Approved Name, and DCFTooltip Dénomination Commune Française.[1][2][3] In the case of the sulfate salt, its USANTooltip United States Adopted Name is mephentermine sulfate and its BANMTooltip British Approved Name is mephentermine sulphate.[3][2][7] Synonyms of mephentermine include mephetedrine and mephenterdrine.[2][7][9] Brand names of mephentermine include Wyamine (USTooltip United States), Fentermin (PTTooltip Portugal), and Mephentine (INTooltip India).[1][2][7]

Availability

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Mephentermine is no longer available in the United States and remains available in few or no other countries.[7][8] However, it appears to remain available in India.[8][7] It has also remained available in Brazil for use in veterinary medicine.[5]

Recreational use

[edit]

Misuse of mephentermine for recreational and/or performance-enhancing purposes has been reported along with addiction and dependence and serious health complications.[16][17][18][19][5][20][21][22][11][23][24][25][26][4] It has been especially encountered in India, the only country in which mephentermine appears to remain available for medical use.[4][7][8]

Exercise and sports

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Mephentermine has been used as a performance-enhancing drug in exercise and sports.[6][11][4] It is on the World Anti-Doping Agency (WADA) list of prohibited substances.[27][26]

Research

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Mephentermine was evaluated in the treatment of congestive heart failure in one small clinical study but was found to be ineffective.[28][29]

Veterinary use

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Mephentermine has been used in veterinary medicine in Brazil under the brand names Potenay and Potemax.[5]

References

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  1. ^ a b c d e f g Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 968. ISBN 978-1-4757-2085-3. Retrieved 28 July 2024.
  2. ^ a b c d e f g h Schweizerischer Apotheker-Verein (2000). Index Nominum 2000: International Drug Directory. Medpharm Scientific Publishers. p. 647. ISBN 978-3-88763-075-1. Retrieved 28 July 2024.
  3. ^ a b c Morton IK, Hall JM (2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Netherlands. p. 175. ISBN 978-94-011-4439-1. Retrieved 28 July 2024.
  4. ^ a b c d e f g h i j k l m n o p Malik YK, Bhardwaj A, Ray A, Malik B, Gupta R (2023). ""Mephentermine Abuse" an Age-old Concern with New Challenges: Review of Literature with Case Series". Annals of Indian Psychiatry. 7 (3): 262–266. doi:10.4103/aip.aip_59_23. ISSN 2588-8366.
  5. ^ a b c d e f g h i j Oliveira MF, Sousa HF, Lima MC, Oliveira JR (March 2011). "Mephentermine: rediscovering its biology and use, misuse and their implications". Braz J Psychiatry. 33 (1): 98–99. doi:10.1590/s1516-44462011000100019. PMID 21537728.
  6. ^ a b c d Docherty JR (June 2008). "Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA)". Br J Pharmacol. 154 (3): 606–622. doi:10.1038/bjp.2008.124. PMC 2439527. PMID 18500382.
  7. ^ a b c d e f g h i j Schweizerischer Apotheker-Verein (2004). Index Nominum: International Drug Directory. Medpharm Scientific Publishers. p. 757. ISBN 978-3-88763-101-7. Retrieved 28 July 2024.
  8. ^ a b c d e f "Mephentermine". drugs.com. 5 August 2020. Archived from the original on 5 August 2020. Retrieved 28 July 2024.
  9. ^ a b c d e "Mephentermine". PubChem. Retrieved 28 July 2024.
  10. ^ a b Brofman BL, Hellerstein HK, Caskey WH (September 1952). "Mephentermine: an effective pressor amine; clinical and laboratory observations". Am Heart J. 44 (3): 396–406. doi:10.1016/0002-8703(52)90261-5. PMID 14952463.
  11. ^ a b c Singh S, Gupta A, Sarkar S (2017). "Mephentermine Dependence in a Young Athlete: Case Report With Review of Literature". J Addict Med. 11 (4): 328–330. doi:10.1097/ADM.0000000000000313. PMID 28574863.
  12. ^ Hsu MC, Lin SF, Kuan CP, Chu WL, Chan KH, Chang-Chien GP (March 2009). "Oxethazaine as the source of mephentermine and phentermine in athlete's urine". Forensic Sci Int. 185 (1–3): e1–5. doi:10.1016/j.forsciint.2008.12.009. PMID 19157735.
  13. ^ Huang WH, Liu CH, Liu RH, Tseng YL (March 2010). "Confirming urinary excretion of mephentermine and phentermine following the ingestion of oxethazaine by gas chromatography-mass spectrometry analysis". J Anal Toxicol. 34 (2): 73–77. doi:10.1093/jat/34.2.73. PMID 20223098.
  14. ^ William F Bruce, Szabo Joseph Lester, Tubis Samuel, U.S. patent 2,597,445 (1952 to Wyeth Corp)
  15. ^ Zenitz BL, Macks EB, Moore ML (1948). "Preparation of α,α-Dimethyl- and N,α,α-Trimethyl-β-cyclohexylethylamine". Journal of the American Chemical Society. 70 (3): 955–957. doi:10.1021/ja01183a019.
  16. ^ Angrist BM, Schweitzer JW, Gershon S, Friedhoff AJ (March 1970). "Mephentermine psychosis: misuse of the Wyamine inhaler". Am J Psychiatry. 126 (9): 1315–1317. doi:10.1176/ajp.126.9.1315. PMID 5413209.
  17. ^ Uday GJ, Josh UG, Bhat SM (January 1988). "Mephentermine dependence with psychosis. A case report". Br J Psychiatry. 152: 129–131. doi:10.1192/bjp.152.1.129. PMID 3167321.
  18. ^ Mendhekar DN, Sharma H, Dali JS (April 1999). "Case report of substance dependence with buprenorphine and mephentermine". Indian J Psychiatry. 41 (2): 160–162. PMC 2962841. PMID 21455380.
  19. ^ de Sousa HF, de Oliveira MF, da Costa Lima MD, de Oliveira JR (June 2010). "Mephentermine dependence without psychosis: a Brazilian case report". Addiction. 105 (6): 1129–1130. doi:10.1111/j.1360-0443.2010.02935.x. PMID 20456293.
  20. ^ Kumar Mattoo S, Parakh P (June 2012). "Mephentermine dependence: an emerging challenge". CNS Neurosci Ther. 18 (6): 509–510. doi:10.1111/j.1755-5949.2012.00328.x. PMC 6493632. PMID 22672305.
  21. ^ Gehlawat P, Singh P, Gupta R, Arya S (2013). "Mephentermine dependence with psychosis". Gen Hosp Psychiatry. 35 (6): 681.e9–10. doi:10.1016/j.genhosppsych.2013.04.019. PMID 23759255.
  22. ^ Gowda GS, Singh A, Ravi M, Math SB (October 2015). "Mephentermine dependence syndrome - A new emerging trend of substance use". Asian J Psychiatr. 17: 101–102. doi:10.1016/j.ajp.2015.07.006. PMID 26236018.
  23. ^ Somani A (November 2020). "Mephentermine dependence in a young Indian adult without psychosis". BMJ Case Rep. 13 (11): e236924. doi:10.1136/bcr-2020-236924. PMC 7607562. PMID 33139366.
  24. ^ Roy P, Shah B, Karia S, Desousa A, Shah N (2021). "Mephentermine abuse - A case report". Indian J Psychiatry. 63 (4): 400–401. doi:10.4103/psychiatry.IndianJPsychiatry_934_20. PMC 8363899. PMID 34456355.
  25. ^ Singal AK, Deepti S, Sharma G, Kothari SS (February 2021). "Herculean mistake: mephentermine associated cardiomyopathy". Phys Sportsmed. 49 (1): 116–122. doi:10.1080/00913847.2020.1763146. PMID 32404042.
  26. ^ a b Bhardwaj A, Yadav J, Arya S, Gupta R (2022). "Mephentermine Misuse: An Impending Crisis among Sportspersons". J Psychoactive Drugs. 54 (2): 196–198. doi:10.1080/02791072.2021.1936701. PMID 34126873.
  27. ^ "The Prohibited List". World Anti Doping Agency. 1 January 2024. Retrieved 28 July 2024.
  28. ^ Goldberg LI (August 1968). "Use of sympathomimetic amines in heart failure". Am J Cardiol. 22 (2): 177–182. doi:10.1016/0002-9149(68)90223-3. PMID 4874959.
  29. ^ Frye RL, Kahler RL, Braunwald E (September 1961). "The ineffectiveness of an inotropic agent, mephentermine (Wyamine), in the treatment of congestive heart failure". Am Heart J. 62 (3): 301–303. doi:10.1016/0002-8703(61)90395-7. PMID 13702337.


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