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Titolo:
Methocinnamox is a potent, long-lasting, and selective antagonist of morphine-mediated antinociception in the mouse: Comparison with clocinnamox, beta-funaltrexamine, and beta-chlornaltrexamine
Autore:
Broadbear, JH; Sumpter, TL; Burke, TF; Husbands, SM; Lewis, JW; Woods, JH; Traynor, JR;
Indirizzi:
Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 t Pharmacol, Ann Arbor, MI 48109 USA Univ Michigan, Sch Med, Dept Psychol, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 ept Psychol, Ann Arbor, MI 48109 USA Univ Bristol, Dept Chem, Bristol, Avon, England Univ Bristol Bristol AvonEngland tol, Dept Chem, Bristol, Avon, England
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 3, volume: 294, anno: 2000,
pagine: 933 - 940
SICI:
0022-3565(200009)294:3<933:MIAPLA>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
IRREVERSIBLE OPIOID ANTAGONIST; GUINEA-PIG BRAIN; GUANOSINE-5'-O-(3-THIO)TRIPHOSPHATE BINDING; VAS-DEFERENS; MU-RECEPTOR; IN-VIVO; AGONISTS; ANALGESIA; MEMBRANES; MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Traynor, JR Univ Michigan, Sch Med, Dept Pharmacol, 1301,MSRBIII, Ann Arbor, MI 48109 USA Univ Michigan 1301,MSRBIII Ann Arbor MI USA 48109 MI 48109 USA
Citazione:
J.H. Broadbear et al., "Methocinnamox is a potent, long-lasting, and selective antagonist of morphine-mediated antinociception in the mouse: Comparison with clocinnamox, beta-funaltrexamine, and beta-chlornaltrexamine", J PHARM EXP, 294(3), 2000, pp. 933-940

Abstract

The irreversible mu-opioid antagonists beta-funaltrexamine (beta-FNA) and beta-chlornaltrexamine (beta-CNA) are important pharmacological tools but have a kappa-agonist activity and, in the latter case, low selectivity. Thiswork examines whether clocinnamox (C-CAM) and the newer analog, methocinnamox (M-CAM), represent improved long-lasting antagonists for examining mu-opioid-mediated effects in vivo. beta-FNA, beta-CNA, C-CAM, and M-CAM were compared after systemic administration in mice and in vitro. beta-FNA and beta-CNA were effective agonists in the writhing assay, reversible by the kappa-antagonist norbinaltorphimine. Neither C-CAM nor M-CAM had agonist activity in vivo. M-CAM was devoid of agonist action at cloned opioid receptors. All four compounds depressed the dose-effect curve for the mu-agonist morphine in the warm-water tail-withdrawal test 1 h after administration; at 48h, recovery was evident. In the writhing assay, the dose-effect curve for morphine was shifted in a parallel fashion in the order M-CAM >> C-CAM > beta-CNA greater than or equal to beta-FNA. In comparison with their ability to shift the dose-effect curve for bremazocine (kappa) and BW373U86 (delta), beta-CNA was the least mu-selective, followed by C-CAM < beta-FNA < M-CAM. M-CAM (1.8 mg/kg) produced a 74-fold increase in the ED50 of morphine while showing no effect on bremazocine or BW373U86 dose-response curves. In binding assays, C-CAM and M-CAM were 8-fold selective for mu- over kappa-receptors, whereas beta-FNA and beta-CNA were mu/delta-, but not mu/kappa selective. However, ex vivo binding assays confirmed the mu-receptor selectivityof M-CAM. M-CAM is thus a potent, long-lasting, and specific antagonist atmu-receptors in vivo that lacks confounding agonist actions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 07:06:29