Effects of the R, R-isomer of labetalol, SCH 19927, in isolated tissues and in spontaneously hypertensive rats during a repeated treatment.
The alpha 1- and beta 1-adrenoceptor blocking activity of the R, R-isomer of labetalol, SCH 19927, was assessed in isolated tissues and compared with that of labetalol. The antihypertensive actions of both compounds were then evaluated during a 10-day dose regimen in spontaneously hypertensive rats (SHR). SCH 19927 produced a competitive alpha 1- and beta 1-blockade in vitro as indicated by the parallel shift to the right of the dose-response curves for norepinephrine and isoprenaline, respectively. SCH 19927 was found 4 times more potent as beta 1-blocker and 6.5 times less potent as alpha 1-blocker than labetalol. In conscious SHR, both SCH 19927 and labetalol produced long-lasting antihypertensive effects during the 10-day period of repeated administration with 10 mg/kg p.o. No tolerance to the antihypertensive activity occurred during the treatment. These findings suggest that SCH 19927 is more potent as a beta-blocker than as an alpha-blocker in isolated tissues and produces an effective antihypertensive activity during a repeated dose regimen.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007741:Labetalol / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013237:Stereoisomerism; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011433:Propranolol; D007741:Labetalol; D009638:Norepinephrine; D010646:Phentolamine