Selectivity and specificity for alpha 1-adrenoceptor blocking activity of R(-)- and S(+)-YM-12617 orally administered to pithed, spontaneously hypertensive rats.
The selectivity and specificity for alpha 1-adrenoceptor blocking activity of the optical isomers of YM-12617 have been examined in pithed, spontaneously hypertensive rats. R(-)-YM-12617 and prazosin (1 mg kg-1 p.o.) produced 360- and 88-fold rightward shifts, respectively, of the dose-response curve of control to phenylephrine, whereas S(+)-YM-12617 (1 mg kg-1 p.o.) failed to cause a shift. Based on dose ratio, R(-)-YM-12617 was 320 times more potent as an alpha 1-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 alpha 1-adrenoceptor blocking activity and its activity was specific for alpha 1-adrenoceptors.
D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D013237:Stereoisomerism; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D000096926:Benzenesulfonamides
D000317:Adrenergic alpha-Antagonists; D013449:Sulfonamides; C044648:YM 12617; D000096926:Benzenesulfonamides