Reference

A difference in mode of antagonism between optical isomers of a potent selective alpha1-adrenoceptor blocker (YM-12617) and norepinephrine in isolated rabbit iris dilator and aorta

A difference in mode of antagonism between optical isomers of a potent selective alpha1-adrenoceptor blocker (YM-12617) and norepinephrine in isolated rabbit iris dilator and aorta. Takayanagi, Issei; Konno, Fukio; Kameda, Hiroyuki; Kubo, Haruichi; Furukawa, Akira; Toyoda, Toshie (Sch. Pharm. Sci., Toho Univ., Chiba 274, Japan). Jpn. J. Pharmacol., 42(4), 579-82 (English) 1986. CODEN: JJPAAZ. ISSN: 0021-5198. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Optical isomers of YM 12617, a potent and selective a-adrenoceptor blocker, were tested on the rabbit iris dilator and aorta. The order of potency was R(-)-isomer [106463-17-6] > racemate [106463-18-7] > S(+)-isomer [106463-19-8]. The R(-)-isomer and racemate behaved an an essentially irreversible antagonist to norepinephrine in the iris dilator where the efficacy of norepinephrine was small, although the S(+)-isomer was a competitive antagonist. These drugs behaved as a competitive antagonist of norepinephrine in the aorta where the efficacy of norepinephrine was large.

Selectivity and specificity for a1-adrenoceptor blocking activity of R(-)- and S(+)-YM-12617 orally administered to pithed, spontaneously hypertensive rats

Selectivity and specificity for a1-adrenoceptor blocking activity of R(-)- and S(+)-YM-12617 orally administered to pithed, spontaneously hypertensive rats. Honda, Kazuo; Momose, Noriko; Nakagawa, Chieko (Dep. Pharmacol., Yamanouchi Pharm. Co. Ltd., Tokyo 174, Japan). J. Pharm. Pharmacol., 39(4), 316-18 (English) 1987. 106463-19-8 and 106463-17-6 which are cas registry numbers are also used here. CODEN: JPPMAB. ISSN: 0022-3573. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The selectivity and specificity of a1-adrenoceptor blocking activity of the optical isomers of YM-12617 have been examd. in pithed, spontaneously hypertensive rats. R(-)-YM-12617 [106463-17-6] and prazosin (1 mg/kg orally) produced 360- and 88-fold rightward shifts, resp., of the dose-response curve of control to phenylephrine, whereas S(+)-YM-12617 [106463-19-8] (1 mg/kg-1 orally) failed to cause a shift. Based on dose ratio, R(-)-YM-12617 was 320 times more potent as an a1-adrenoceptor antagonist than S(+)-YM-12617. This potency ratio corresponded to that formed in an in- vitro study. Both R(-)- and S(+)-YM-12617 hardly affected the UK-14304, angiotensin II, vasopressin and isoprenaline dose-response curves. These results suggest that R(-)-YM-12617 exerted selective a1-adrenoceptor blocking activity and its activity was specific for a1-adrenoceptors. .