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Titolo:
XANOMELINE - A NOVEL MUSCARINIC RECEPTOR AGONIST WITH FUNCTIONAL SELECTIVITY FOR M(1) RECEPTORS
Autore:
SHANNON HE; BYMASTER FP; CALLIGARO DO; GREENWOOD B; MITCH CH; SAWYER BD; WARD JS; WONG DT; OLESEN PH; SHEARDOWN MJ; SWEDBERG MDB; SUZDAK PD; SAUERBERG P;
Indirizzi:
ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS INDIANAPOLIS IN 46285 NOVO NORDISK AS,CNS DIV DK-2760 MALOV DENMARK
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 1, volume: 269, anno: 1994,
pagine: 271 - 281
SICI:
0022-3565(1994)269:1<271:X-ANMR>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
LOWER ESOPHAGEAL SPHINCTER; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; SENILE DEMENTIA; RAT-BRAIN; BINDING-SITES; HIGH-AFFINITY; ADRENERGIC PROJECTION; NERVOUS-SYSTEM; M3 RECEPTORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
80
Recensione:
Indirizzi per estratti:
Citazione:
H.E. Shannon et al., "XANOMELINE - A NOVEL MUSCARINIC RECEPTOR AGONIST WITH FUNCTIONAL SELECTIVITY FOR M(1) RECEPTORS", The Journal of pharmacology and experimental therapeutics, 269(1), 1994, pp. 271-281

Abstract

Xanomeline adiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine] has been evaluated as a muscarinic receptor agonist. In vitro, xanomeline hadhigh affinity for muscarinic receptors in brain homogenates, but had substantially less or no affinity for a number of other neurotransmitter receptors and uptake sites. In cells stably expressing genetic mi receptors, xanomeline increased phospholipid hydrolysis in CHO, BHK andA9 L cells to 100, 72 and 55% of the nonselective agonist carbachol. In isolated tissues, xanomeline had high affinity for M(1) receptors in the rabbit vas deferens (IC50 = 0.006 nM), low affinity for M(2) receptors in guinea pig atria (EC(50) = 3 mu M), was a weak partial agonist in guinea pig ileum and was neither an agonist nor antagonist in guinea pig bladder. In vivo, xanomeline increased striatal levels of dopamine metabolites, presumably by acting at M(1) heteroreceptors on dopamine neurons to increase dopamine release. In contrast, xanomeline had only a relatively small effect on acetylcholine levels in brain, indicating that it is devoid of actions at muscarinic autoreceptors. In the gastrointestinal tract, xanomeline inhibited small intestinal and colonic motility, but increased small intestinal transmural potential difference. In contrast to the nonselective muscarinic agonist oxotremorine, xanomeline did not produce salivation, tremor nor hypothermia; it did, however, increase heart rate. The present data are consistent with the interpretation that xanomeline is a novel muscarinic receptor agonist with functional selectivity for M(1) muscarinic receptors bothin vitro and in vivo.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 09:36:29