title: Dexmedetomidine produces a hypnotic-anesthetic action in rats via activation of central alpha-2 adrenoceptors.
abstract: Dexmedetomidine, a highly selective and potent alpha-2 adrenoceptor agonist, reduces halothane anesthetic requirements by over 90% in rats. The present study examined whether dexmedetomidine produces a hypnotic-anesthetic action in rats. Dexmedetomidine induced a hypnotic-anesthetic state in rats characterized by loss of righting reflex at doses greater than or equal to 0.1 mg/kg. This response was dose-dependent between 0.1 and 3 mg/kg. Alpha-2 adrenoceptor antagonists that cross the blood-brain barrier (antipamezole and idazoxan) decreased the hypnotic-anesthetic action of dexmedetomidine in a dose-dependent fashion. In contrast, the alpha-2 antagonist, L-659,066, which does not penetrate into the CNS did not affect dexmedetomidine-induced hypnosis. Antagonists for the other adrenoceptors not only failed to reduce the hypnotic-anesthetic action of dexmedetomidine but in some cases even potentiated this effect. Thus, prazosin, an alpha-1 adrenoceptor antagonist, significantly enhanced the hypnotic-anesthetic property of dexmedetomidine. Antagonists with beta-2 receptor blocking properties also enhanced dexmedetomidine-induced hypnosis. Selective beta-1 receptor antagonists did not affect the hypnotic action of dexmedetomidine. These results suggest that dexmedetomidine produces a hypnotic-anesthetic action in rats via activation of central alpha-2 adrenoceptors.
authors.affiliation: Department of Anesthesiology, Sun Yat-Sen University of Medical Sciences, Guangzhou, People's Republic of China.
authors.forename: V A
authors.initials: VA
authors.lastname: Doze
authors.forename: B X
authors.initials: BX
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Maze
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000777:Anesthetics / Q000037:antagonists & inhibitors; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000037:antagonists & inhibitors; D019329:Idazoxan; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D020926:Medetomidine; D009126:Muscle Relaxation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D000777:Anesthetics; D004146:Dioxanes; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; C050701:atipamezole; D020926:Medetomidine; D019329:Idazoxan