Abecarnil

Abecarnil (ZK-112,119) is an anxiolytic drug from the β-Carboline family. It is one of a relatively recently developed class of medicines known as the nonbenzodiazepines, which have similar effects to the older benzodiazepine group, but with quite different chemical structures. It is a partial agonist acting selectively at the benzodiazepine site of the GABAA receptor.[1]

Abecarnil
Clinical data
ATC code
  • none
Pharmacokinetic data
Elimination half-life3.4 hours (IV), 7 hours (oral)
Identifiers
IUPAC name
  • propan-2-yl 4-(methoxymethyl)-6-(phenylmethoxy) -9H-pyrido[5,4-b]indole-3-carboxylate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC24H24N2O4
Molar mass404.466 g·mol−1
3D model (JSmol)
SMILES
  • COCc3c(C(=O)OC(C)C)ncc4[nH]c2ccc(OCc1ccccc1)cc2c34
InChI
  • InChI=1S/C24H24N2O4/c1-15(2)30-24(27)23-19(14-28-3)22-18-11-17(29-13-16-7-5-4-6-8-16)9-10-20(18)26-21(22)12-25-23/h4-12,15,26H,13-14H2,1-3H3 Y
  • Key:RLFKILXOLJVUNF-UHFFFAOYSA-N Y
  (verify)

Abecarnil was originally developed as an anti-anxiety drug, but has not as yet been commercially developed for use in humans, instead so far mainly being used for research into the development of other new sedative and anxiolytic drugs. Investigations are continuing into its actions and it looks likely to be developed for use both in the treatment of anxiety,[2] and as a less addictive substitute drug for the treatment of benzodiazepine[3] and alcohol[4] addiction. Abecarnil may also have fewer problems of tolerance and withdrawal problems compared to nonselective full agonist benzodiazepine acting drugs.[5]

Abecarnil is a relatively subtype-selective drug which produces primarily anxiolytic effects, with comparatively less sedative or muscle relaxant properties,[6][7] and does not significantly potentiate the effects of alcohol.[8]

The abuse potential of abecarnil is thought to be less than that of benzodiazepines,[9] with only mild withdrawal symptoms noted after abrupt discontinuation of treatment.[10]

See also

References
  1. Ozawa, M; Nakada, Y; Sugimachi, K; Yabuuchi, F; Akai, T; Mizuta, E; Kuno, S; Yamaguchi, M (Mar 1994). "Pharmacological characterization of the novel anxiolytic beta-carboline abecarnil in rodents and primates". Japanese Journal of Pharmacology. 64 (3): 179–87. doi:10.1254/jjp.64.179. PMID 7912751.
  2. Aufdembrinke B (1998). "Abecarnil, a new beta-carboline, in the treatment of anxiety disorders". British Journal of Psychiatry. 34 (34): 55–63. doi:10.1192/S0007125000293537. PMID 9829018.
  3. Pinna G, Galici R, Schneider HH, Stephens DN, Turski L (Mar 1997). "Alprazolam dependence prevented by substituting with the beta-carboline abecarnil". Proceedings of the National Academy of Sciences of the United States of America. 94 (6): 2719–23. Bibcode:1997PNAS...94.2719P. doi:10.1073/pnas.94.6.2719. PMC 20156. PMID 9122263.
  4. Jung ME, Wallis CJ, Gatch MB, Lal H (Jun 2000). "Abecarnil and alprazolam reverse anxiety-like behaviors induced by ethanol withdrawal". Alcohol. 21 (2): 161–8. doi:10.1016/S0741-8329(00)00079-3. PMID 10963939.
  5. Löscher W, Hönack D (April 1992). "Withdrawal precipitation by benzodiazepine receptor antagonists in dogs chronically treated with diazepam or the novel anxiolytic and anticonvulsant beta-carboline abecarnil". Naunyn Schmiedebergs Arch. Pharmacol. 345 (4): 452–60. doi:10.1007/BF00176624. PMID 1352384. S2CID 20486955.
  6. Krause W, Schutt B, Duka T (May 1990). "Pharmacokinetics and acute toleration of the beta-carboline derivative abecarnil in man". Arzneimittelforschung. 40 (5): 529–32. PMID 1974428.
  7. Duka T, Schutt B, Krause W, Dorow R, McDonald S, Fichte K (Apr 1993). "Human studies on abecarnil, a new beta-carboline anxiolytic: safety, tolerability and preliminary pharmacological profile". British Journal of Clinical Pharmacology. 35 (4): 386–94. doi:10.1111/j.1365-2125.1993.tb04155.x. PMC 1381549. PMID 8097921.
  8. Stephens DN, Schneider HH, Kehr W, Andrews JS, Rettig KJ, Turski L, Schmiechen R, Turner JD, Jensen LH, et al. (Apr 1990). "Abecarnil, a metabolically stable, anxioselective beta-carboline acting at benzodiazepine receptors". Journal of Pharmacology and Experimental Therapeutics. 253 (1): 334–43. PMID 1970361.
  9. Sannerud CA, Ator NA, Griffiths RR (Oct 1992). "Behavioral pharmacology of abecarnil in baboons: self-injection, drug discrimination and physical dependence". Behavioural Pharmacology. 3 (5): 507–516. doi:10.1097/00008877-199210000-00009. PMID 11224153. S2CID 32081258.
  10. Ballenger JC, McDonald S, Noyes R, Rickels K, Sussman N, Woods S, Patin J, Singer J (1991). "The first double-blind, placebo-controlled trial of a partial benzodiazepine agonist abecarnil (ZK 112-119) in generalized anxiety disorder". Psychopharmacology Bulletin. 27 (2): 171–9. PMID 1681563.
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