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Titolo:
SLOW DISSOCIATION OF LONG-ACTING CA2-3 PN200-110 BINDING-SITES IN MEMBRANES OF RAT HEARTS AND BRAINS( ANTAGONIST AMLODIPINE FROM H)
Autore:
SUGIYAMA K; QU YL; MARUYAMA K; HATTORI K; WATANABE K; NAGATOMO T;
Indirizzi:
NIIGATA COLL PHARM,DEPT PHARMACOL,5-13-2 KAMISHINEI CHO NIIGATA 95021JAPAN NIIGATA COLL PHARM,DEPT PHARMACOL NIIGATA 95021 JAPAN TSUBAME ROSAI HOSP,DIV CARDIOVASC RES LABS TSUBAME NIIGATA 95912 JAPAN
Titolo Testata:
Biological & pharmaceutical bulletin
fascicolo: 2, volume: 19, anno: 1996,
pagine: 195 - 198
SICI:
0918-6158(1996)19:2<195:SDOLCP>2.0.ZU;2-Z
Fonte:
ISI
Lingua:
ENG
Soggetto:
CHANNEL BLOCKING PROPERTIES; DIHYDROPYRIDINE RECEPTORS; SMOOTH-MUSCLE; CALCIUM; SM-6586; ISOMERS; ASSAY;
Keywords:
AMLODIPINE; H-3 PN200-110; RAT HEART; RAT BRAIN; CA2+ ANTAGONIST; SLOW DISSOCIATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
19
Recensione:
Indirizzi per estratti:
Citazione:
K. Sugiyama et al., "SLOW DISSOCIATION OF LONG-ACTING CA2-3 PN200-110 BINDING-SITES IN MEMBRANES OF RAT HEARTS AND BRAINS( ANTAGONIST AMLODIPINE FROM H)", Biological & pharmaceutical bulletin, 19(2), 1996, pp. 195-198

Abstract

The dissociation rate of amlodipine ((+/-)-3-ethyl 5-methyl yl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate benzenesulfonate) from rat heart and brain membranes preincubated with drugs and washed out with buffer was assessed by radioligand binding assay using H-3-PN200-110 asa radioligand. The remaining KCl-induced contraction in rat aortic strips washed out after treatment with this drug and the pK(i) (inhibition constant) values of the drug were compared with those of nisoldipine. nifedipine, manidipine and benidipine. The inhibition of H-3-PN200-110 binding induced by nifedipine was reversed by washing whereas thatinduced by amIodipine, manidipine, and benidipine was not readily reversed under these conditions. When rat aortic strips were pretreated with Ca2+ antagonists, the rank order of the inhibition of contractionsinduced by 50 mM KCl was manidipine = benidipine > amiodipine > nisoldipine > nifedipine, even though Ca2+ antagonists were not present in the extracellular medium. The pK(i) values of amlodipine in the heart and brain were 6.86 and 7.31, respectively, and these values were lower than those of the other Ca2+ antagonists. There was a good correlation between the potency of the inhibition of H-3-PN200-110 binding by drugs after the washout of membranes and the inhibition exerted by the drugs in contractions induced by 50 mM KCl after the washout of tissues, although this residual inhibition was not correlated with pK(i) values. Thus, these results suggest that amlodipine has a very slow rate of dissociation from H-3-PN200-110 binding; sites, as do manidipine and benidipine, and this property may explain its long-lasting antihypertensive effect.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 21:16:15