Intrinsic sympathomimetic activity of labetalol.
In intact cats, cumulative doses (0.1-10 mg/kg i.v.) of labetalol produced dose-dependent decreases in heart rate and arterial blood pressure and dose-dependently reduced i.v. phenylephrine induced pressor responses. In spinal cats devoid of resting sympathetic tone, labetalol (1 mg/kg i.v.) produced a sustained elevation of heart rate and a transient fall in arterial blood pressure. In reserpine-pretreated, adrenalectomized cats, labetalol produced quantitatively the same effects as in spinal cats, indicating that the cardiovascular effects observed in cats with no resting sympathetic tone are due to a direct action of labetalol rather than via catecholamine release. The elevated heart rate due to labetalol in spinal cats was reduced by subsequent administration of the beta-adrenergic receptor antagonist, propranolol. Further, pretreatment with propranolol prevented the tachycardic and depressor effects of labetalol in spinal cats. In a separate group of spinal cats, labetalol administered in cumulative doses of up to 1 mg/kg i.v., produced graded increases in heart rate and also dose dependently reduced i.v. isoproterenol-induced tachycardic responses. Pindolol, a beta-adrenergic receptor antagonist with partial beta-agonist activity, produced similar effects in spinal cats at cumulative doses of 1-30 micrograms/kg. These results indicate that the alpha- and beta-adrenergic receptor antagonist, labetalol possesses partial beta-adrenergic receptor agonist activity. This intrinsic sympathomimetic action of labetalol appears to be more sustained on cardiac than on vascular beta-adrenergic receptors.
A S
AS
Tadepalli
P J
PJ
Novak
D000311:Adrenal Glands / Q000502:physiology; D000318:Adrenergic beta-Agonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007741:Labetalol / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology
D000318:Adrenergic beta-Agonists; D012110:Reserpine; D011433:Propranolol; D010869:Pindolol; D007545:Isoproterenol; D007741:Labetalol; D009638:Norepinephrine