Alpha 2-adrenoceptors and vigilance in cats: antagonism of medetomidine sedation by atipamezole.
In order to evaluate the effect of a specific alpha 2-adrenoceptor antagonist, atipamezole, on vigilance, adult cats with implanted electrodes for polygraphy were tested in a double-blind Latin square design. The standard clinical dose (0.1 mg/kg i.m.) of the specific alpha 2-adrenoceptor agonist, medetomidine, promptly induced stuporous sedation. Atipamezole, given 30 min later at 0.2, 0.4 or 0.8 mg/kg i.m., reversed the sedation within 3 min, resulting in complete awareness of the animal. After the small dose of atipamezole, arousal with some motor excitation continued for 6 h, whereas after the larger doses, the physiological sleep-wake cycle returned earlier. Used alone, the preferred dose, 0.4 mg/kg atipamezole i.m., allowed physiological sleep within 33 +/- 9 min, compared to 22 +/- 3 min after saline. Atipamezole thus proved to be a most effective antagonist to sedation with alpha 2-adrenoceptor agonist drugs, without disturbing excitatory effects. Specific alpha 2-adrenoceptor modulating drugs have evident clinical application, as antidotes to overdosage of alpha 2-adrenoceptor agonists, or to terminate their effect after surgical procedures.
Stenberg
D
D
Department of Physiology, University of Helsinki, Finland.
Porkka-Heiskanen
T
T
Toppila
J
J
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D002415:Cats; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D004566:Electrodes; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D012890:Sleep / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; C050701:atipamezole; D020926:Medetomidine