Pagoclone

Effects

Overview

An anxiolytic drug related to zopiclone with no sedative or hypnotic qualities. Has been investigated as a possible alcohol replacement. Related in structure and effect to Zopiclone and Zolpidem. TS

Pagoclone is an anxiolytic agent from the cyclopyrrolone family, related to better-known drugs such as the sleeping medication zopiclone. It was synthesized by a French team working for Rhone-Poulenc & Rorer S.A. Pagoclone belongs to the class of nonbenzodiazepines, which have similar effects to the older benzodiazepine group, but with quite different chemical structures. It was never commercialised.[1] WP

It binds with roughly equivalent high affinity (0.7–9.1 nM) to the benzodiazepine binding site of human GABAA receptors containing either an α1, α2, α3 or α5 subunit. It is a partial agonist at α1-, α2- and α5-containing GABAA receptors and a full agonist at receptors containing an α3 subunit. In rats 5′-hydroxypagoclone was identified as a major metabolite. This metabolite has a considerably greater efficacy at the α1 subtype than the parent compound and was shown to have significant anxiolytic-like activity and to produce sedation. In contrast to zopiclone, pagoclone produces anxiolytic effects with little sedative or amnestic actions at low doses (0.3mg to 1.2mg per day).[2][3][4] WP

The pharmacologist David Nutt has suggested pagoclone as a possible base from which to make a better social drug, as it produces the positive effects of alcohol, such as relaxation and sociability, but without also causing the negative effects like aggression, amnesia, nausea, loss of coordination and liver damage. Its effect can be quickly reversed by the action of flumazenil, which is already used as an antidote to benzodiazepine overdose. Nutt has published studies praising the potential of pagoclone which were financed by Indevus which was seeking funding for a possible production of the compound. The long-term safety of pagoclone has not been assessed. The abuse potential of pagoclone has been assessed as being similar to, or slightly less than that of diazepam and it would also be expected to be somewhat safer due to its relatively weaker sedative effects, but development of pagoclone as a commercial drug would still be unlikely due to concerns about abuse.[5][6][7] WP⚠ Wikipedia itself has flagged this text: citation needed.

Pagoclone was trialed as a drug to improve speech fluency as a treatment for stuttering, but research for this application was discontinued following disappointing results in Phase II clinical trials.[8] WP

History

Legal status

Pharmacology

Chemistry

Formula

C23H22ClN3O2 PC

CAS number

133737-32-3 PC

Molar mass (g/mol)

407.9 PC

IUPAC name (computed by PubChem)

2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-3H-isoindol-1-one PC

SMILES

CC(C)CCC(=O)CC1C2=CC=CC=C2C(=O)N1C3=NC4=C(C=C3)C=CC(=N4)Cl PC

InChIKey

HIUPRQPBWVEQJJ-UHFFFAOYSA-N PC

PubChem CID

131664

IUPAC name

2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)isoindolin-1-one WP

Pop culture

No references added yet.

References

1. Other 2-Amino naphthyridine derivative, its preparation and its use
2. Journal / agency Atack JR, Pike A, Marshall G, Stanley J, Lincoln R, Cook SM, Lewis RT, Blackaby WP, Goodacre SC, McKernan RM, Dawson GR, Wafford KA, Reynolds DS. The in vivo properties of pagoclone in rat are most likely mediated by 5'-hydroxy pagoclone. Neuropharmacology. May 2006. doi:10.1016/j.neuropharm.2005.11.014 · PMID 16430927
3. Journal / agency Atack JR. The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics. Expert Opinion on Investigational Drugs. May 2005. doi:10.1517/13543784.14.5.601 · PMID 15926867
4. Journal / agency Atack JR. Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site. Current Drug Targets. CNS and Neurological Disorders. August 2003. doi:10.2174/1568007033482841 · PMID 12871032
5. Journal / agency Nutt DJ. Alcohol alternatives--a goal for psychopharmacology?. Journal of Psychopharmacology. May 2006. doi:10.1177/0269881106063042 · PMID 16574703
6. Journal / agency Lingford-Hughes A, Wilson SJ, Feeney A, Grasby PG, Nutt DJ. A proof-of-concept study using [11C]flumazenil PET to demonstrate that pagoclone is a partial agonist. Psychopharmacology. August 2005. doi:10.1007/s00213-005-0060-1 · PMID 15986186
7. Journal / agency de Wit H, Vicini L, Haig GM, Hunt T, Feltner D. Evaluation of the abuse potential of pagoclone, a partial GABAA agonist. Journal of Clinical Psychopharmacology. June 2006. doi:10.1097/01.jcp.0000218983.61683.96 · PMID 16702891
8. Journal / agency Maguire G, Franklin D, Vatakis NG, Morgenshtern E, Denko T, Yaruss JS, Spotts C, Davis L, Davis A, Fox P, Soni P, Blomgren M, Silverman A, Riley G. Exploratory randomized clinical study of pagoclone in persistent developmental stuttering: the EXamining Pagoclone for peRsistent dEvelopmental Stuttering Study. Journal of Clinical Psychopharmacology. February 2010. doi:10.1097/jcp.0b013e3181caebbe · PMID 20075648

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