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Titolo:
PHARMACOLOGY OF BUTYLTHIO[2.2.2] (LY297802 NNC11-1053) - A NOVEL ANALGESIC WITH MIXED MUSCARINIC RECEPTOR AGONIST AND ANTAGONIST ACTIVITY/
Autore:
SHANNON HE; SHEARDOWN MJ; BYMASTER FP; CALLIGARO DO; DELAPP NW; GIDDA J; MITCH CH; SAWYER BD; STENGEL PW; WARD JS; WONG DT; OLESEN PH; SUZDAK PD; SAUERBERG P; SWEDBERG MDB;
Indirizzi:
ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS INDIANAPOLIS IN 46285 NOVO NORDISK AS,HLTH CARE DISCOVERY DK-2760 MALOV DENMARK
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 281, anno: 1997,
pagine: 884 - 894
SICI:
0022-3565(1997)281:2<884:POB(N->2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT STRIATAL MEMBRANES; RABBIT VAS-DEFERENS; GUINEA-PIG; BINDING-SITES; ACETYLCHOLINE-RECEPTORS; HIGH-AFFINITY; SPINAL-CORD; OPIATE RECEPTOR; MESSENGER-RNAS; NERVOUS-SYSTEM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
81
Recensione:
Indirizzi per estratti:
Citazione:
H.E. Shannon et al., "PHARMACOLOGY OF BUTYLTHIO[2.2.2] (LY297802 NNC11-1053) - A NOVEL ANALGESIC WITH MIXED MUSCARINIC RECEPTOR AGONIST AND ANTAGONIST ACTIVITY/", The Journal of pharmacology and experimental therapeutics, 281(2), 1997, pp. 884-894

Abstract

Butylthio[2.2.2], -1,2,5-thiadiazol-3-yl)-1-azabicyclo[2.2.2]octane; LY297802/NNC11-1053) is a muscarinic receptor ligand which is equiefficacious to morphine in producing antinociception. In vitro, butylthio[2.2.2] had high affinity for muscarinic receptors in brain homogenates, but had substantially less or no affinity for several other neurotransmitter receptors and uptake sites. In isolated tissues, butylthio[2.2.2] was an agonist with high affinity for M-1 receptors in the rabbitvas deferens (IC50 = 0.33 nM), but it was an antagonist at M-2 receptors in guinea pig atria (pA(2) = 6.9) and at M-3 receptors in guinea pig urinary bladder (pA(2) = 7.4) and a weak partial agonist in guinea pig ileum, which contains a heterogeneous population of muscarinic receptors. In viveo, butylthio[2,2.2] was without effect on acetylcholine, dopamine and serotonin Levels in rat brain. Moreover, butylthio[2.2.2] did not decrease charcoal meal transit in mice, nor did it significantly alter heart rate in rats. Further, butylthio[2.2,2] did not produce parasympathomimetic effects such as salivation or tremor in mice, but it antagonized salivation and tremor produced by the nonselective muscarinic agonist oxotremorine. The present data demonstrate that butylthio[2.2.2] is a novel muscarinic receptor mixed agonist/antagonist and its pharmacological profile suggests that it may have clinical utility in the management of pain as an alternative to opioids.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 08:34:24