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Titolo:
alpha(2)-adrenoceptor antagonist properties of OPC-28326, a novel selective peripheral vasodilator
Autore:
Orito, K; Kishi, M; Imaizumi, T; Nakazawa, T; Hashimoto, A; Mori, T; Kambe, T;
Indirizzi:
Otsuka Pharmaceut Co Ltd, Inst New Drug Res 1, Kawauchi, Tokushima 7710192, Japan Otsuka Pharmaceut Co Ltd Kawauchi Tokushima Japan 7710192 7710192, Japan
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 4, volume: 134, anno: 2001,
pagine: 763 - 770
SICI:
0007-1188(200110)134:4<763:AAPOOA>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT VAS-DEFERENS; RECEPTOR SUBTYPE; ALPHA-2-ADRENOCEPTOR SUBTYPES; ALPHA-2 ADRENOCEPTORS; FUNCTIONAL EVIDENCE; PULMONARY-ARTERY; AGONISTS; VASOCONSTRICTION; INHIBITION; LIMBS;
Keywords:
OPC-28326; peripheral vasodilator; alpha(2)-adrenoceptor; antagonist; postsynaptic; yohimbine; vas deferens; pithed rat; blood pressure; mydriasis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
28
Recensione:
Indirizzi per estratti:
Indirizzo: Mori, T Otsuka Pharmaceut Co Ltd, Inst New Drug Res 1, Kawauchi, Tokushima7710192, Japan Otsuka Pharmaceut Co Ltd Kawauchi Tokushima Japan 7710192 , Japan
Citazione:
K. Orito et al., "alpha(2)-adrenoceptor antagonist properties of OPC-28326, a novel selective peripheral vasodilator", BR J PHARM, 134(4), 2001, pp. 763-770

Abstract

1 Antagonistic properties of OPC-28326 ([4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl-aminobenzoyl)] piperidine hydrochloride monohydrate), a selective peripheral vasodilator, were investigated by analysing the data from functional studies in various tissues from the rat and binding studies of the drug to alpha (2)-adrenoceptor subtypes.2 Using a human recombinant receptor and rat kidney cortex, we found that OPC-28326 displays affinities to alpha (2A)-, alpha (2B)- and alpha (2C)-adrenoceptors with K-i values of 2040, 285, and 55 nM, respectively. The K-i values of yohimbine for alpha (2A)-, alpha (2B)-, and alpha (2C)-adrenoceptors were 3.0, 2.0 and 11.0 nM, respectively.3 B-HT 920, an alpha (2)-adrenoceptor agonist, produced a pressor responsevia peripheral postsynaptic a2-adrenoceptor stimulation (thought to be an alpha (2B)-subtype) in a reserpine-pretreated pithed rat preparation. OPC-28326 (3-30 mg kg(-1), i.v.) and yohimbine (0.3-3 mg kg(-1), i.v.) caused dose-dependent rightward shift in the pressor dose-response curve induced by B-HT 920. The apparent pA(2) values were 1.55 (0.87-2.75, 95% confidence interval) and 0.11 (0.06-0.21) mg kg(-1), respectively. The potency of OPC-28326 was about 14 times less than that of yohimbine.4 Clonidine inhibited the tension developed by electrical stimulation, of the rat vas deferens, by its peripheral presynaptic alpha (2A/D)-adrenoceptor action. OPC-28326 (1-100 muM) and yohimbine (10-1000 nM) caused a rightward shift in the concentration-response curve of clonidine. The pA(2), values were 5.73 (5.54-5.91) and 7.92 (7.84-8.01), respectively, providing evidence for a potency of OPC-28326 of about 155 times less than that of yohimbine.5 Mydriasis was induced by brimonidine via stimulation of central alpha (2A/D)-adrenoceptors in anaesthetized rats. Intravenous OPC-28326 had no effect on this action, even at a very high dose of 10 mg kg(-1) i.v., while yohimbine (0.1-0.3 mg kg(-1) i.v.) inhibited mydriasis in a dose-dependent manner, indicating that OPC-28326 was at least 100 times less potent than yohimbine in regard to the anti-mydriatic effect.6 These data suggest that OPC-28326 preferentially exerts peripheral and postsynaptic antagonistic actions on the alpha (2B)- and alpha (2C)-adrenoceptor subtypes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 22:14:33