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Titolo:
SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety
Autore:
Wood, MD; Reavill, C; Trail, B; Wilson, A; Stean, T; Kennett, GA; Lightowler, S; Blackburn, TP; Thomas, D; Gager, TL; Riley, G; Holland, V; Bromidge, SM; Forbes, IT; Middlemiss, DN;
Indirizzi:
SmithKline Beecham Pharmaceut, Dept Neurosci Res, Harlow CM19 5AW, Essex, England SmithKline Beecham Pharmaceut Harlow Essex England CM19 5AW ssex, England SmithKline Beecham Pharmaceut, Dept Discovery Chem, Harlow CM19 5AW, Essex, England SmithKline Beecham Pharmaceut Harlow Essex England CM19 5AW ssex, England
Titolo Testata:
NEUROPHARMACOLOGY
fascicolo: 2, volume: 41, anno: 2001,
pagine: 186 - 199
SICI:
0028-3908(200108)41:2<186:SAS5RI>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
HALOPERIDOL-INDUCED CATALEPSY; NEUROLEPTIC-INDUCED AKATHISIA; ATYPICAL ANTIPSYCHOTIC-DRUGS; NUCLEUS-ACCUMBENS; RAT-BRAIN; ANTAGONIST; SEROTONIN; LOCALIZATION; MECHANISMS; CHLOROPHENYLPIPERAZINE;
Keywords:
SB-243213; 5-HT2C receptor; anxiety; tolerance; withdrawal; feeding; seizures; catalepsy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Wood, MD SmithKline Beecham Pharmaceut, Dept Neurosci Res, New Frontiers Sci Pk,3rdAve, Harlow CM19 5AW, Essex, England SmithKline Beecham PharmaceutNew Frontiers Sci Pk,3rd Ave Harlow Essex England CM19 5AW
Citazione:
M.D. Wood et al., "SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety", NEUROPHARM, 41(2), 2001, pp. 186-199

Abstract

SB-243213 (5-methyl-1-[[-2-[(2-methyl-3-pyridyl)oxyl-5-pyridyl]carbamoyl]-6-trifluoromethylindoline hydrochloride) is a new, selective 5-hydroxytryptamine (5-HT)(2C) receptor inverse agonist. SB-243213 has high affinity for the human 5-HT2C receptor (pK(i) 9.37) and greater than a 100-fold selectivity over a wide range of neurotransmitter receptors, enzymes and ion channels. In in vitro functional studies, SB-243213 acted as an inverse agonist at the human 5-HT2C receptor with a pK(b) of 9.8. In in vivo studies, SB-243213 was a potent inhibitor of central 5-HT2C receptor-mediated function in rats, blocking meta-chlorophenylpiperazine-induced hypolocomotion with an ID50 of 1.1 mg/kg p.o. and a long duration of action (>8 h). In rats, SB-243213 exhibited anxiolytic-like activity in both the social interaction and Geller-Seifter conflict tests. Importantly, unlike diazepam, chronic administration of SB-243213 did not result in the development of either tolerance to the anxiolytic-like effects or withdrawal anxiogenesis. Furthermore, in rodents, SB-243213 did not affect seizure threshold, did not increase body weight or induce catalepsy, but attenuated the haloperidol-induced catalepsy. SB-243213 did not affect amphetamine-, MK-801- or phencyclidine-induced hyperactivity. In conclusion, SB-243213 may possess an improved anxiolytic profile compared to benzodiazepines. SB-243213 also modulates dopaminergic transmission, lacks pro-psychotic properties and may have utility in the treatment of schizophrenia and motor disorders. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/01/20 alle ore 12:20:42