Pagoclone 4716261 173818315 2007-11-26T03:47:46Z 198.142.36.62 {{drugbox | IUPAC_name = 2-(7-chloro-1,8-naphthyridin-2-yl)-3-(5-methyl-<br>2-oxo-hexyl)-3''H''-isoindol-1-one | image = Pagoclone.svg | CAS_number = 133737-32-3 | ATC_prefix = | ATC_suffix = | PubChem = 131664 | DrugBank = | C = 23 | H = 22 | Cl = 1 | N = 3 | O = 2 | molecular_weight = 407.893 g/mol | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = <!-- A / B / C / D / X --> | pregnancy_category= | legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> | legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> | legal_status = | routes_of_administration = }} '''Pagoclone''' is an [[anxiolytic]] drug from the [[cyclopyrrolone]] family, which is related to other more well known drugs such as the sleeping medication [[zopiclone]]. It is one of a relatively recently developed class of medicines known as the [[nonbenzodiazepine]]s, which have similar effects to the older [[benzodiazepine]] group, but with quite different [[chemical structure]]s. Pagoclone was originally developed as an anti-anxiety drug, but never commercialised. It is a [[partial agonist]] acting at [[GABA A receptor|GABA<sub>A</sub>]] [[receptor (biochemistry)|receptors]] in the brain. In contrast to zopiclone, pagoclone produces anxiolytic effects with little or no [[sedative]] or [[amnestic]] actions at low doses.<ref>Atack JR. Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site. ''Current Drug Targets. CNS and Neurological Disorders''. 2003 Aug;2(4):213-32.</ref> This is because pagoclone is a subtype-selective drug which binds primarily to the α2/α3 subtypes of the GABA<sub>A</sub> receptor which are responsible for the anti-anxiety effects of these kind of drugs, but has relatively little efficacy at the α1 subtype which produces the sedative and memory loss effects.<ref>Atack JR. The benzodiazepine binding site of GABA(A) receptors as a target for the development of novel anxiolytics. ''Expert Opinion on Investigational Drugs''. 2005 May;14(5):601-18.</ref> [[David Nutt]] from the [[University of Bristol]] 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]].<ref>{{cite journal | author= Nutt DJ| title= For "Critique and Commentaries" section of the Journal of Psychopharmacology: Alcohol alternatives - a goal for psychopharmacology? | journal=Journal of Psychopharmacology| year=2006 | volume=20 | pages=318–320 | doi=10.1177/0269881106063042}}</ref> Dr. Nutt has published studies<ref>{{cite journal | author= Lingford-Hughes A ''et al.'' | title= A proof-of-concept study using [<sup>11</sup>C]flumazenil PET to demonstrate that pagoclone is a partial agonist | journal=Psychopharmacology| year=2005 | volume=180 | pages=1–3 | pmid=15986186 | doi=10.1007/s00213-005-0060-1}}</ref> praising the potential of pagoclone which were financed by [[Indeveus]] which holds the patents to the pharmaceutical and is, as of Spring 2006, seeking funding for a possible production of the compound. The significance of this is undetermined, but it should be noted that 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,<ref>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''. 2006 Jun;26(3):268-73.</ref> but development of pagoclone as a recreational drug would still be unlikely due to concerns about abuse. Pagoclone is also being trialed as a drug to improve a [[stutter|stammerer]]'s speech fluency.[http://www.google.com/patents?id=gOIUAAAAEBAJ&printsec=abstract&zoom=4&dq=pagoclone] ==See also== * [[Bretazenil]] * [[Stuttering]] * [[Basal ganglia]] * [[GABA]] ==References== {{Reflist}} {{Anxiolytics}} {{pharma-stub}} ==External links== *[http://video.google.com/videoplay?docid=7814001879103559464 Video on stuttering and pagoclone] *[http://video.google.com/videoplay?docid=9165066264092615016 Stuttering case report: Astonishing recovery (news video)] [[Category:Cyclopyrrolones]]