Xiaoying Qiao, Ikuo Norota and Masao Endoh*
Department of Pharmacology, Yamagata University School of Medicine, 2-2-2
lida-nishi, Yamagata 990-9585, Japan
*Corresponding author.ÊÊFAX:+81-23-628-5235
E-mail: mendou@med.id.yamagata-u.ac.jp
Abstract: Influence of JTH-601 [N-(3-hydroxy-6-methoxy-2,4,5-trimethylbenzyl)-N-methyl-2-(4-hydroxy-2-isopropyl-5-methylphenoxy)ethylamine
hemifumarate], a selective a1-adrenoceptor
antagonist, on a1-mediated positive
inotropic effect (PIE) was studied in isolated rabbit papillary muscle (1ÊHz
at 37¡C). JTH-601 (0.1-10ÊmM) shifted the concentration-response
curve (CRC) for PIE of phenylephrine mediated by a1-adrenoceptor
(with timolol at 1ÊmM) to the right and downward.
In the presence of 100ÊnM WBÊ4101, an a1A
antagonist, the shift to the right disappeared and JTH-601 (1-3ÊmM)
shifted CRC for phenylephrine downward. The antagonistic action of JTH-601
was unchanged by 100ÊnM (+)-niguldipine, another a1A
antagonist. Following pretreatment with 10ÊmM
chloroethylclonidine, an a1B antagonist,
the shift of CRC for phenylephrine to the right disappeared and JTH-601
(3-10ÊmM) shifted CRC downward. Antagonistic
action of JTH-601 (3ÊmM) was unaltered by 100ÊnM
BMYÊ7378, an a1D antagonist. JTH-601
(10ÊmM) had no effect on b-mediated
PIE of isoproterenol. These results indicate that JTH-601 exerts an inhibitory
action on a1-mediated PIE through
antagonism of a1A- and/or a1B-adrenoceptors
in rabbit ventricular myocardium. As an a1
antagonist, JTH-601 is much less potent in rabbit ventricular muscle than
in smooth muscle.
Keywords: a1-Adrenoceptor, Positive
inotropic effect, Selective of a1-adrenoceptor
antagonist, JTH-601,
Rabbit ventricular myocardium
Copyright© The Japanese Pharmacological Society 2000
[Back to TOC]