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Titolo:
Xanomeline, an M-1/M-4 preferring muscarinic cholinergic receptor agonist,produces antipsychotic-like activity in rats and mice
Autore:
Shannon, HE; Rasmussen, K; Bymaster, FP; Hart, JC; Peters, SC; Swedberg, MDB; Jeppesen, L; Sheardown, MJ; Sauerberg, P; Fink-Jensen, A;
Indirizzi:
Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USAEli Lilly & Co Indianapolis IN USA 46285 Labs, Indianapolis, IN 46285 USA Novo Nordisk AS, Hlth Care Discovery, DK-2760 Malov, Denmark Novo Nordisk AS Malov Denmark DK-2760 Discovery, DK-2760 Malov, Denmark
Titolo Testata:
SCHIZOPHRENIA RESEARCH
fascicolo: 3, volume: 42, anno: 2000,
pagine: 249 - 259
SICI:
0920-9964(20000505)42:3<249:XAMPMC>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
CONDITIONED AVOIDANCE-RESPONSE; A10 DOPAMINE NEURONS; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; BEHAVIORAL SYMPTOMS; NUCLEUS-ACCUMBENS; CLIMBING BEHAVIOR; ADENYLATE-CYCLASE; HALOPERIDOL; INHIBITION;
Keywords:
antipsychotic-like activity; behavior; electrophysiology; microdialysis; schizophrenia; xanomeline;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Social & Behavioral Sciences
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Shannon, HE Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA Eli Lilly & Co Indianapolis IN USA 46285 apolis, IN 46285 USA
Citazione:
H.E. Shannon et al., "Xanomeline, an M-1/M-4 preferring muscarinic cholinergic receptor agonist,produces antipsychotic-like activity in rats and mice", SCHIZOPHR R, 42(3), 2000, pp. 249-259

Abstract

Xanomeline is an M-1/M-4 preferring muscarinic receptor agonist which decreased psychotic behaviors in patients with Alzheimer's disease, suggesting that xanomeline might be useful in the treatment of psychotic symptoms in patients with schizophrenia. The purpose of the present studies was, therefore, to compare the pharmacologic profile of xanomeline with that of known antipsychotic drugs. Electrophysiologically, xanomeline, after both acute and chronic administration in rats, inhibited A10 but not A9 dopamine cells in a manner which was blocked by the muscarinic receptor antagonist scopolamine. Behaviorally, xanomeline, like haioperidol, clozapine and olanzapine, blocked dopamine agonist-induced turning in unilateral 6-hydroxydopamine-lesioned rats, as well as apomorphine-induced climbing in mice. However, unlike the dopamine antagonist antipsychotic haloperidol, xanomeline did not produce catalepsy in rats. Moreover, xanomeline, like haloperidol, clozapine and olanzapine, inhibited conditioned avoidance responding in rats, an effect which also was blocked by scopolamine. The present results thus demonstrate that xanomeline has a pharmacologic profile which is similar to that ofthe atypical antipsychotics clozapine and olanzapine, thus indicating thatxanomeline has the potential to be a novel approach in the treatment of psychotic symptoms in patients with schizophrenia. (C) 2000 Elsevier Science B.V. All rights reserved.

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Documento generato il 26/01/20 alle ore 00:51:14