Adimolol, a long acting beta-adrenoceptor blocker in man.
A comparative study in eight healthy normotensive males of the effects on blood pressure, heart rate and beta-adrenoceptor function following single oral doses of adimolol (600 mg), propranolol (240 mg) and placebo. Both active treatments produced small but significant reductions in blood pressure and heart rate, supine and erect. These effects persisted for up to 7 days after adimolol. The heart rate increases following both dynamic exercise and intravenous isoprenaline were attenuated by both propranolol and adimolol. With adimolol evidence of functional beta-adrenoceptor antagonism was sustained for up to 7 days. Lymphocyte beta-adrenoceptor binding studies showed that both adimolol and propranolol significantly reduced affinity for beta-adrenoceptors. In addition, adimolol significantly reduced receptor number and even by 3 days after dosing Bmax had only returned to half the control value. In a small sub-group of subjects there was no evidence to suggest that adimolol had additional alpha-adrenoceptor antagonist properties. Adimolol was detected in plasma for up to 3 days after dosing. The mean terminal elimination half-life was 14 h, compared to 3 h for propranolol. This study confirms that adimolol has prolonged beta-adrenoceptor antagonist activity with effects persisting for up to 7 days after a single dose. The reduction in beta-adrenoceptor number following adimolol suggests that this prolonged effect may not be solely due to competitive antagonism but may additionally depend upon non-competitive antagonism at beta-adrenoceptors.
D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011412:Propanolamines / Q000378:metabolism / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D011943:Receptors, Adrenergic, beta / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; C045342:adimolol