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Titolo:
IN-VIVO PHARMACOLOGY OF BUTYLTHIO[2.2.2] (LY297802 NNC11-1053), AN ORALLY ACTING ANTINOCICEPTIVE MUSCARINIC AGONIST/
Autore:
SHANNON HE; WOMER DE; BYMASTER FP; CALLIGARO DO; DELAPP NC; MITCH CH; WARD JS; WHITESITT CA; SWEDBERG MDB; SHEARDOWN MJ; FINKJENSEN A; OLESEN PH; RIMVALL K; SAUERBERG P;
Indirizzi:
ELI LILLY & CO,LILLY RES LABS,LILLY CORP CTR INDIANAPOLIS IN 46285 NOVO NORDISK AS,HLTH CARE DISCOVERY DK-2760 MALOV DENMARK
Titolo Testata:
Life sciences
fascicolo: 13-14, volume: 60, anno: 1997,
pagine: 969 - 976
SICI:
0024-3205(1997)60:13-14<969:IPOB(N>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTORS; LOCALIZATION; BRAIN; INHIBITION; ANALGESIA;
Keywords:
BUTYLTHIO[2.2.2]; ANTINOCICEPTION; M2 ANTAGONIST;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
24
Recensione:
Indirizzi per estratti:
Citazione:
H.E. Shannon et al., "IN-VIVO PHARMACOLOGY OF BUTYLTHIO[2.2.2] (LY297802 NNC11-1053), AN ORALLY ACTING ANTINOCICEPTIVE MUSCARINIC AGONIST/", Life sciences, 60(13-14), 1997, pp. 969-976

Abstract

Butylthio[2.2.2] (LY297802 / NNC11-1053) is a mixed muscarinic cholinergic receptor agonist/antagonist that produces antinociception in mice and rats. As such, butylthio[2.2.2] may have therapeutic utility in the treatment of pain. Butylthio[2.2.2] was fully efficacious in the mouse grid shock, writhing tail-flick and hot plate tests with ED(50) values ranging from 1.5 to 12.2 mg/kg after oral administration. In contrast, the ED(50) values for morphine ranged from 7.3 to 72 mg/kg after oral administration. Scopolamine was a competitive antagonist of theantinociceptive effects of butylthio[2.2.2]. Butylthio[2.2.2] did notproduce either salivation or tremor at therapeutic doses; rather, there was a 50- to >100-fold separation between therapeutic doses and doses which produced side-effects. Butylthio[2.2.2] had high affinity formuscarinic receptors, but little if any affinity for other neurotransmitter receptors or uptake sites. In isolated tissues, butylthio[2.2.2] was an agonist with high affinity at M1 receptors in rabbit vas deferens, an antagonist at M2 receptors in guinea pig atria as well as an antagonist at M3 receptors in guinea pig urinary bladder. Although it has been suggested that M1 receptors mediate the antinociceptive effects of muscarinic agonists, M1 efficacy is not a requirement for antinociception, and, in vivo, the antinociceptive effects of muscarinic agonists are blocked by the intrathecal administration of pertussis toxin, indicating the involvement of m2 or m4 receptors. Since butylthio[2.2.2] is an M2 antagonist, antinociception is therefore most likely mediated by m4 receptors. Butylthio[2.2.2] is currently undergoing clinical development as a novel analgesic.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 12:59:08