Amineptine

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Amineptine
Clinical data
Trade namesSurvector, others
Other namesS-1694
Routes of
administration		Oral
ATC code
Legal status
Legal status
Renal
Identifiers
  • 7-[(10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5-yl)amino]heptanoic acid
JSmol)
SMILES
  • O=C(O)CCCCCCNC1c2ccccc2CCc2ccccc21
  • InChI=1S/C22H27NO2/c24-21(25)13-3-1-2-8-16-23-22-19-11-6-4-9-17(19)14-15-18-10-5-7-12-20(18)22/h4-7,9-12,22-23H,1-3,8,13-16H2,(H,24,25) checkY
  • Key:ONNOFKFOZAJDHT-UHFFFAOYSA-N checkY
  (verify)

Amineptine, formerly sold under the brand name Survector among others, is an atypical antidepressant of the tricyclic antidepressant (TCA) family.[4][5] It acts as a selective and mixed dopamine reuptake inhibitor and releasing agent, and to a lesser extent as a norepinephrine reuptake inhibitor.[4][5]

Amineptine was developed by the French Society of Medical research in the 1960s.

Servier,[7] amineptine soon gained a reputation for abuse due to its short-lived, but pleasant, stimulant
effect experienced by some patients.

After its release into the European market, cases of hepatotoxicity emerged, some serious. This, along with the potential for abuse, led to the suspension of the French marketing authorization for Survector in 1999.[8]

Amineptine is illegal in both Germany and the United States.

Medical uses

Amineptine was approved in France for severe

clinical depression of endogenous origin in 1978.[9]

Contraindications

  • Chorea
  • Hypersensitivity: Known hypersensitivity to amineptine, in particular antecedents of hepatitis after dosage of the product.
  • MAO inhibitors

Precautions for use

Warnings and precautions before taking amineptine:[10]

Effects on the fetus

  • Lacking information in humans
  • Non-
    teratogenic
    in rodents

Side effects

Dermatological

Severe

acne due to amineptine was first reported in 1988 by various authors—Grupper, Thioly-Bensoussan, Vexiau, Fiet, Puissant, Gourmel, Teillac, Levigne, to name a few—simultaneously[11][12][13][14][15] in the same issue of Annales de Dermatologie et de Vénéréologie and in the 12 March 1988 issue of The Lancet.[16] A year later, Dr Martin-Ortega and colleagues in Barcelona, Spain reported a case of "acneiform eruption" in a 54-year-old woman whose intake of amineptine was described as "excessive."[17] One year after that, Vexiau and colleagues reported six women, one of whom never admitted to using amineptine, getting severe acne concentrated in the face, back and thorax, the severity of which varied with the dosage.[18] Most of them were treated unsuccessfully with isotretinoin (Accutane) for about 18 months; two of the three that discontinued amineptine experienced a reduction in cutaneous symptoms, with the least affected patient going into remission.[18]

Psychiatric

Psychomotor excitation can very rarely occur with this drug.

Abuse and dependence

The risk of

bulimia appeared.[21]

Withdrawal

Pharmacodependence is very common with amineptine compared to other antidepressants.[22] A variety of psychological symptoms can occur during withdrawal from amineptine,[23] such as anxiety and agitation.[24]

Cardiovascular

Very rarely:

Hepatic

Amineptine can rarely cause hepatitis, of the cytolytic, cholestatic varieties.[25] Amineptine-induced hepatitis, which is sometimes preceded by a rash, is believed to be due to an immunoallergic reaction.[26] It resolves upon discontinuation of the offending drug.[25] The risk of getting this may or may not be genetically determined.[27]

Additionally, amineptine is known to rarely elevate transaminases, alkaline phosphatase, and bilirubin.[28]

Mixed hepatitis, which is very rare, generally occurs between the 15th and 30th day of treatment of amineptine. Often preceded by sometimes intense abdominal pains, nausea, vomiting or a rash, the jaundice is variable. Hepatitis is either of mixed type or with cholestatic prevalence. The evolution was, in all the cases, favorable to the discontinuation of the drug. The mechanism is discussed (immunoallergic and/or toxic).[29]

In circa 1994 Spain, there was a case associating acute pancreatitis and mixed hepatitis, after three weeks of treatment.[30]

Lazaros and colleagues at the Western Attica General Hospital in Athens, Greece reported two cases of drug induced hepatitis 18 and 15 days of treatment.[31]

One case of cytolytic hepatitis occurred after ingestion of only one tablet.[32]

Gastrointestinal

  • Acute pancreatitis (very rare) A case associating acute pancreatitis and mixed hepatitis after three weeks of treatment.[30]

Immunological

A case of

anaphylactic shock in a woman who had been taking amineptine has been reported.[33]

Pharmacology

Pharmacodynamics

Amineptine[34]
Site Ki (nM) Species Ref
SERTTooltip Serotonin transporter >100,000 (IC50) Rat [35]
NETTooltip Norepinephrine transporter 10,000 (IC50)
3,560		 Rat
Canine		 [35][36]
[37]
DATTooltip Dopamine transporter 1,000–1,400 (IC50)
3,330		 Rat
Canine		 [35][38][36]
[37]
5-HT1A >100,000 Rat [39]
5-HT2A 74,000 Rat [39]
α1 >100,000 Rat [39]
α2 >100,000 Rat [39]
β
 >100,000 Rat [39]
D1
 >100,000 Canine [35]
D2
 >100,000 Rat/canine [35][39]
H1 >100,000
13,000		 Rat
Guinea pig		 [39]
[40]
mAChTooltip Muscarinic acetylcholine receptor >100,000 Rat [39]
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.

Amineptine

serotonin, adrenergic, dopamine, histamine, and muscarinic acetylcholine receptors.[39][40][41] The major metabolites of amineptine have similar activity to that of the parent compound, albeit with lower potency.[41]

No human data appear to be available for binding or inhibition of the monoamine transporters by amineptine.[42]

Pharmacokinetics

elimination half-life of amineptine is about 0.80 to 1.0 hours and that of its major metabolite is about 1.5 to 2.5 hours.[2][3] Due to their very short elimination half-lives, amineptine and its major metabolite do not accumulate significantly with repeated administration.[2]

Society and culture

Brand names

Amineptine has been sold under a variety of brand names including Survector, Maneon, Directim, Neolior, Provector, and Viaspera.

It had been proposed that Amineptine become a Schedule I controlled substance in the United States in July 2021.[43] This announcement was followed by the placement of Amineptine into Schedule I. [44]

Research

Wakefulness

Amineptine shows wakefulness-promoting effects in animals and might be useful in the treatment of narcolepsy.[45][46][47][48]

References

  1. ^ Anvisa (31 March 2023). "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 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  2. ^
    S2CID 25992333
    .
  3. ^
    S2CID 31069503
    .
  4. ^
    S2CID 32862145
    .
  5. ^
    S2CID 26550661
    .
  6. ^ DE 2011806, Fresnes C, Malen JS, "New Tricyclic Derivatives and Process for their Manufacture", issued 3 December 1981, assigned to Science Union et Cie. Societe Francaise de Recherche Medical, Suresnes (Frankreich) 
  7. ISBN 978-0-8155-1144-1. Archived from the original on 23 October 2005. Retrieved 29 October 2005.[page needed
    ]
  8. ^ "Docket No. 02N-0101". U.S. Food and Drug Administration. 9 April 2002. Retrieved 30 January 2014.
  9. ^ Doctissimo (2005). "SURVECTOR – Amineptine" (in French). Archived from the original on 9 March 2005. Retrieved 27 October 2005.
  10. ^ Amineptine Medication – Uses, Side Effects and Precautions of Amineptine. Health-care-information.org. Retrieved on 28 September 2013
  11. PMID 2977079
    .
  12. PMID 2977080
    .
  13. PMID 2977081
    .
  14. PMID 2977082
    .
  15. PMID 2977083
    .
  16. S2CID 32936080
    .
  17. PMID 2534534
    .
  18. ^
    S2CID 39394890
    .
  19. PMID 2260032
    .
  20. PMID 7227285
    .
  21. PMID 2265603
    .
  22. PMID 9231505
    .
  23. PMID 2260032
    .
  24. PMID 2265603
    .
  25. ^
    PMID 7454584
    .
  26. PMID 3044468
    .
  27. PMID 9204405
    .
  28. PMID 10533145
    .
  29. ^ Concours Med 1982; 104:5733-5734[verification needed]
  30. ^
    PMID 8189020
    .
  31. PMID 8884331
    .
  32. PMID 1397859
    .
  33. PMID 2488491
    .
  34. ^ Roth BL, Driscol, J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  35. ^
    S2CID 10947713
    .
  36. ^
    PMID 3708219
    .
  37. ^
    PMID 11382857
    .
  38. PMID 8676127
    .
  39. ^
    PMID 6464782
    .
  40. ^
    PMID 6141518
    .
  41. ^
    S2CID 23014661
    .
  42. PMID 19557250
    .
  43. ^ "2021 - Placement of Amineptine in Schedule I". Archived from the original on 3 December 2021. Retrieved 30 November 2021.
  44. ^ "Federal Register". Federal Register. National Archives & Drug Enforcement Administration. 17 November 2022.
  45. ISBN 978-3-319-23738-1
    .
  46. PMID 18078360
    .
  47. PMID 23065655
    .
  48. PMID 11382857
    .
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