Central beta- and alpha-adrenolytic activities of adimolol.
The central adrenergic blocking activity of adimolol (ADL) was studied in rats and mice in the tests which can differentiate beta-, alpha 1-, and alpha 2-adrenolytic effects. Clenbuterol- and salbutamol-induced sedation in rats (open field test) and clenbuterol-induced hyperthermia (at high ambient temperature) were antagonized by low doses of ADL (0.1-1.0 mg/kg ip). ADL (10 mg/kg ip) attenuated the clonidine-induced aggression in mice, and its higher doses (20 and 40 mg/kg ip) depressed the hind limb flexor reflex of the spinal rat and counteracted the stimulatory action of clonidine. ADL at doses from 2.5 to 40 mg/kg ip affected neither the clonidine-induced sedation in rats and mice (locomotor activity, open field test), nor the hyperthermia (at high temperature). The hypothermia (at a room temperature of 21 degrees C) induced by clonidine was partially antagonized. The Ki values for ADL displacement of 3H-dihydroalprenolol and 3H-prazosin binding in the rat cerebral cortex were 1.2 nM and 951 nM respectively. These results indicate that ADL is a potent antagonist of central beta-adrenoceptors and has a weaker alpha 1-adrenolytic action. The central alpha 2-antagonistic effect is either very weak or absent.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000374:Aggression / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D002976:Clenbuterol / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D003655:Decerebrate State; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D013045:Species Specificity
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011955:Receptors, Drug; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; C045342:adimolol; D003000:Clonidine; D009638:Norepinephrine; D002976:Clenbuterol