Abecarnil
{{short description|Chemical compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Verifiedfields = changes
| verifiedrevid = 477237117
| IUPAC_name = propan-2-yl 4-(methoxymethyl)-6-(phenylmethoxy) -9H-pyrido[5,4-b]indole-3-carboxylate
| image = Abecarnil-2D-by-AHRLS-2012.png
| tradename =
| pregnancy_category =
| legal_status =
| routes_of_administration =
| bioavailability =
| metabolism =
| elimination_half-life = 3.4 hours (IV), 7 hours (oral)
| excretion =
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 111841-85-1
| ATC_prefix = none
| ATC_suffix =
| PubChem = 65914
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 59323
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = IZM1PNJ3JL
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02594
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 454095
| C=24 | H=24 | N=2 | O=4
| smiles = COCc3c(C(=O)OC(C)C)ncc4[nH]c2ccc(OCc1ccccc1)cc2c34
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RLFKILXOLJVUNF-UHFFFAOYSA-N
}}
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.{{cite journal | vauthors = Ozawa M, Nakada Y, Sugimachi K, Yabuuchi F, Akai T, Mizuta E, Kuno S, Yamaguchi M | title = Pharmacological characterization of the novel anxiolytic beta-carboline abecarnil in rodents and primates | journal = Japanese Journal of Pharmacology | volume = 64 | issue = 3 | pages = 179–187 | date = March 1994 | pmid = 7912751 | doi = 10.1254/jjp.64.179 | doi-access = free }}
Development
Abecarnil was originally developed as an anti-anxiety drug, but has not as yet been commercially developed for use in humans. It has mainly been used for research into the development of other new sedative and anxiolytic drugs. Investigations are continuing into its actions, and it is likely to be developed for use in the treatment of anxiety{{cite journal | vauthors = Aufdembrinke B | title = Abecarnil, a new beta-carboline, in the treatment of anxiety disorders | journal = The British Journal of Psychiatry. Supplement | volume = 34 | issue = 34 | pages = 55–63 | year = 1998 | pmid = 9829018 | doi = 10.1192/S0007125000293537 | s2cid = 24311570 }} and as a less addictive substitute drug for the treatment of benzodiazepine{{cite journal | vauthors = Pinna G, Galici R, Schneider HH, Stephens DN, Turski L | title = Alprazolam dependence prevented by substituting with the beta-carboline abecarnil | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 6 | pages = 2719–2723 | date = March 1997 | pmid = 9122263 | pmc = 20156 | doi = 10.1073/pnas.94.6.2719 | doi-access = free | bibcode = 1997PNAS...94.2719P }} and alcohol{{cite journal | vauthors = Jung ME, Wallis CJ, Gatch MB, Lal H | title = Abecarnil and alprazolam reverse anxiety-like behaviors induced by ethanol withdrawal | journal = Alcohol | volume = 21 | issue = 2 | pages = 161–168 | date = June 2000 | pmid = 10963939 | doi = 10.1016/S0741-8329(00)00079-3 }} addiction.
Pharmacology
Abecarnil is a relatively subtype-selective drug that produces primarily anxiolytic effects, with comparatively fewer sedative or muscle relaxant properties.{{cite journal | vauthors = Krause W, Schütt B, Duka T | title = Pharmacokinetics and acute toleration of the beta-carboline derivative abecarnil in man | journal = Arzneimittel-Forschung | volume = 40 | issue = 5 | pages = 529–532 | date = May 1990 | pmid = 1974428 }}{{cite journal | vauthors = Duka T, Schütt B, Krause W, Dorow R, McDonald S, Fichte K | title = Human studies on abecarnil a new beta-carboline anxiolytic: safety, tolerability and preliminary pharmacological profile | journal = British Journal of Clinical Pharmacology | volume = 35 | issue = 4 | pages = 386–394 | date = April 1993 | pmid = 8097921 | pmc = 1381549 | doi = 10.1111/j.1365-2125.1993.tb04155.x }} Additionally, it does not significantly potentiate the effects of alcohol.{{cite journal | vauthors = Stephens DN, Schneider HH, Kehr W, Andrews JS, Rettig KJ, Turski L, Schmiechen R, Turner JD, Jensen LH, Petersen EN | title = Abecarnil, a metabolically stable, anxioselective beta-carboline acting at benzodiazepine receptors | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 253 | issue = 1 | pages = 334–343 | date = April 1990 | pmid = 1970361 }}
Potential advantages
Abecarnil may have fewer problems with tolerance and withdrawal compared to nonselective full agonist benzodiazepine acting drugs.{{cite journal | vauthors = Löscher W, Hönack D | title = Withdrawal precipitation by benzodiazepine receptor antagonists in dogs chronically treated with diazepam or the novel anxiolytic and anticonvulsant beta-carboline abecarnil | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 345 | issue = 4 | pages = 452–460 | date = April 1992 | pmid = 1352384 | doi = 10.1007/BF00176624 | s2cid = 20486955 }}
The abuse potential of abecarnil is thought to be less than that of benzodiazepines,{{cite journal | vauthors = Sannerud CA, Ator NA, Griffiths RR | title = Behavioral pharmacology of abecarnil in baboons: self-injection, drug discrimination and physical dependence | journal = Behavioural Pharmacology | volume = 3 | issue = 5 | pages = 507–516 | date = October 1992 | pmid = 11224153 | doi = 10.1097/00008877-199210000-00009 | s2cid = 32081258 }} with only mild withdrawal symptoms noted after abrupt discontinuation of treatment.{{cite journal | vauthors = Ballenger JC, McDonald S, Noyes R, Rickels K, Sussman N, Woods S, Patin J, Singer J | title = The first double-blind, placebo-controlled trial of a partial benzodiazepine agonist abecarnil (ZK 112-119) in generalized anxiety disorder | journal = Psychopharmacology Bulletin | volume = 27 | issue = 2 | pages = 171–179 | year = 1991 | pmid = 1681563 }}
Photoswitchable analog
A photoswitchable analog of abecarnil (azocarnil) has been developed to locally and reversibly control neuroinhibition with light in wildtype animals.{{cite journal | vauthors = Maleeva G, Nin-Hill A, Wirth U, Rustler K, Ranucci M, Opar E, Rovira C, Bregestovski P, Zeilhofer HU, König B, Alfonso-Prieto M, Gorostiza P | title = Light-Activated Agonist-Potentiator of GABAA Receptors for Reversible Neuroinhibition in Wildtype Mice | journal = Journal of the American Chemical Society | date = October 2024 | pmid = 39383450 | doi = 10.1021/jacs.4c08446 | pmc = 11503767 }}
See also
References
{{reflist}}
{{Anxiolytics}}
{{GABAAR PAMs}}
Category:Indole ethers at the benzene ring