Resolution and pharmacological properties of the enantiomers of the potent alpha-adrenoceptor antagonist 1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine.
Resolution of the optical isomers of the alpha-adrenoceptor antagonist IP-66 (1-[2-ethoxy-2-(3'-pyridyl)ethyl]-4-(2'-methoxy-phenyl)piperazine) and its intermediate IP-30 (1-[2-hydroxy-2-(3'-pyridyl)ethyl]-4- (2'-methoxy-phenyl)piperazine have been carried out. Optical purity was assayed by high-pressure liquid chromatography. The antagonistic potencies of racemic mixtures and stereoisomers toward phenylephrine- and norepinephrine-induced contraction in isolated rat aortic strips have been compared. (+)-IP-66 and (+)-IP-30 were resp. 363 and 170 times more potent than respective (-) isomers in eliciting competitive alpha 1-adrenoceptor blockade. Similarly IP-66 (+) or (+/-) were extremely more effective than the (-) isomer in antagonizing norepinephrine-induced pressor responses in pithed rat.
D000317:Adrenergic alpha-Antagonists / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D014661:Vasoconstriction / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D010656:Phenylephrine; C040940:IP 66; D009638:Norepinephrine