1. Dexmedetomidine produces a hypnotic-anesthetic action in rats via activation of central alpha-2 adrenoceptors
- Author
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Van A. Doze, Bing-Xue Chen, and Mervyn Maze
- Subjects
Male ,medicine.medical_specialty ,Muscle Relaxation ,Adrenergic beta-Antagonists ,Pharmacology ,Dioxanes ,Idazoxan ,Internal medicine ,medicine ,Prazosin ,Animals ,Hypnotics and Sedatives ,Dexmedetomidine ,Anesthetics ,business.industry ,Antagonist ,Imidazoles ,Rats, Inbred Strains ,Medetomidine ,Receptors, Adrenergic, alpha ,Rats ,Anesthesiology and Pain Medicine ,Endocrinology ,Mechanism of action ,Anesthetic ,medicine.symptom ,Halothane ,business ,Adrenergic alpha-Agonists ,Injections, Intraperitoneal ,medicine.drug - 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.
- Published
- 1989