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Titolo:
The muscarinic receptor agonist BuTAC, a novel potential antipsychotic, does not impair learning and memory in mouse passive avoidance
Autore:
Rasmussen, T; Fink-Jensen, A; Sauerberg, P; Swedberg, MDB; Thomsen, C; Sheardown, MJ; Jeppesen, L; Calligaro, DO; DeLapp, NW; Whitesitt, C; Ward, JS; Shannon, HE; Bymaster, FP;
Indirizzi:
Novo Nordisk AS, Hlth Care Discovery, DK-2760 Malov, Denmark Novo Nordisk AS Malov Denmark DK-2760 Discovery, DK-2760 Malov, Denmark Eli Lilly & Co, Lilly Res Labs, Neurosci Res Div, Indianapolis, IN 46285 USA Eli Lilly & Co Indianapolis IN USA 46285 Div, Indianapolis, IN 46285 USA
Titolo Testata:
SCHIZOPHRENIA RESEARCH
fascicolo: 1-2, volume: 49, anno: 2001,
pagine: 193 - 201
SICI:
0920-9964(20010415)49:1-2<193:TMRABA>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
PREFRONTAL CORTEX; MICE; SCHIZOPHRENIA; ANTAGONISTS; HALOPERIDOL; RISPERIDONE; OLANZAPINE; MODULATION; COGNITION; CLOZAPINE;
Keywords:
BuTAC; clozapine; olanzapine; muscarinic agonists; passive avoidance; schizophrenia;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Social & Behavioral Sciences
Life Sciences
Citazioni:
29
Recensione:
Indirizzi per estratti:
Indirizzo: Fink-Jensen, A Bispebjerg Hosp, Dept Psychiat E, 23 Bispebjerg Bakke, DK-2400 Copenhagen NV, Denmark Bispebjerg Hosp 23 Bispebjerg Bakke Copenhagen Denmark NV
Citazione:
T. Rasmussen et al., "The muscarinic receptor agonist BuTAC, a novel potential antipsychotic, does not impair learning and memory in mouse passive avoidance", SCHIZOPHR R, 49(1-2), 2001, pp. 193-201

Abstract

(5R.6R)-6-(3-butylthio-1,2,5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane) (BuTAC) is a novel. selective muscarinic receptor ligand with partial agonist mode of action at muscarinic M-2 and M-4 and antagonist mode of action atM-1, M-3 and M-5 receptor subtypes in cloned cell lines. BuTAC exhibits functional dopamine receptor antagonism despite its lack of affinity for dopamine receptors, and parasympathomimetic effects in mice are produced only at doses well beyond the doses exhibiting the antipsychotic-like effects. Inthe present study we investigated the effects of BuTAC and the antipsychotic compounds clozapine, sertindole and olanzapine using one trial passive avoidance with mice as a model of learning and memory. Pharmacologically relevant doses of BuTAC and reference antipsychotics were identified, based oninhibition of apomorphine-induced climbing in mice as an assay measuring antidopaminergic potency. When ratios between the minimum effective dose (MED) for impairment of retention in passive avoidance and the MED for inhibition of apomorphine-induced climbing were calculated. BuTAC displayed a highratio of > 10, compared with clozapine (0.3), sertindole (3) and olanzapine (3). These data suggest that BuTAC is a potential novel antipsychotic which may have favourable effects on aspects of learning and memory. (C) 2001 Elsevier Science B.V. All rights reserved.

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Documento generato il 18/01/20 alle ore 13:12:26