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Titolo:
Pharmacological characterization of (10bS)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline oxalate (YSL-3S) as a new alpha(2)-adrenoceptor antagonist
Autore:
Chung, SH; Yook, J; Min, BJ; Lee, JY; Lee, YS; Jin, CB;
Indirizzi:
Korea Inst Sci & Technol, Bioanal & Biotransformat Res Ctr, Seoul 130791, South Korea Korea Inst Sci & Technol Seoul South Korea 130791 ul 130791, South Korea Korea Inst Sci & Technol, Med Chem Res Ctr, Seoul 130791, South Korea Korea Inst Sci & Technol Seoul South Korea 130791 ul 130791, South Korea Kyung Hee Univ, Coll Pharm, Seoul 130701, South Korea Kyung Hee Univ Seoul South Korea 130701 Pharm, Seoul 130701, South Korea Hankuk Univ Foreign Studies, Dept Chem, Yongin 449791, South Korea Hankuk Univ Foreign Studies Yongin South Korea 449791 49791, South Korea
Titolo Testata:
ARCHIVES OF PHARMACAL RESEARCH
fascicolo: 4, volume: 23, anno: 2000,
pagine: 353 - 359
SICI:
0253-6269(200008)23:4<353:PCO(>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALPHA-2-ADRENERGIC RECEPTORS; ALPHA-ADRENOCEPTORS; YOHIMBINE; ANTIDEPRESSANTS; BINDING; BRAIN; ACID; RAT;
Keywords:
alpha(2)-Adrenoceptors; depression; YSL-3S; yohimbine; clonidine; [H-3]rauwolscine; [H-3]cytisine; cerebral cortex; vas deferens;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Jin, CB Korea Inst Sci & Technol, Bioanal & Biotransformat Res Ctr, POB 131,Cheongryang, Seoul 130650, South Korea Korea Inst Sci & Technol POB 131,Cheongryang Seoul South Korea 130650
Citazione:
S.H. Chung et al., "Pharmacological characterization of (10bS)-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline oxalate (YSL-3S) as a new alpha(2)-adrenoceptor antagonist", ARCH PH RES, 23(4), 2000, pp. 353-359

Abstract

alpha(2)-Adrenoceptor antagonists, which can enhance synaptic norepinephrine levels by blocking feedback inhibition processes, are potentially usefulin the treatment of disease states such as depression, memory impairment, impotence and sexual dysfunction. (10bS)-1,2,3,5,6,10b-Hexahydropyrrolo[2,1-a]isoquinoline oxalate (YSL-3S) was evaluated in several in vitro biological tests to establish its pharmacological profile of activities as an alpha(2)-adrenoceptor antagonist. Saturation binding assay revealed that [H-3]rauwolscine bound to the alpha(2)-adrenoceptors with a Kd value of 6.3 +/- 0.5 nM and a Bmax value of 251 +/- 39 fmol/mg protein in rat cortical synaptic membranes. Competitive binding assay showed that YSL-3S inhibited the binding of [H-3]rauwolscine (1 nM) in a concentration-dependent manner with a Ki value of 98.2 +/- 12.1 nM while it did not inhibit the binding of [H-3]cytisine (1.25 nM) to neuronal nicotinic cholinergic receptors. The Ki values of yohimbine, clonidine and norepinephrine for [H-3]rauwolscine binding were 15.8 +/- 1.0, 40.1 +/- 5.9 and 40.0 +/- 11.5 nM, respectively. In addition, the binding affinity of YSL-3S for a(2)-adrenoceptors was higher than that of its antipode and the racemic mixture. The functional activity of YSL-3S at the presynaptic alpha(2)-adrenoceptors was assessed using the prostatic portion of the rat vas deferens. Clonidine inhibited field-stimulated contractions of the vas deference in a dose-dependent manner. The presence of YSL-3S or yohimbine caused a parallel, rightward the dose-response curveof clonidine in a dose-dependent manner, indicating an antagonistic actionat the presynaptic alpha(2)-adrenoceptors. The pA(2) values of yohimbine and YSL-3S were 7.66 +/- 0.13 and 6.64 +/- 0.18, respectively. The results indicate that YSL-3S acts as a competitive antagonist at presynaptic alpha(2)-adrenoceptors with a potency approximately ten times lower than yohimbine, but is devoid of binding affinity for neuronal nicotinic cholinergic receptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 16:36:19