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Pharmacological evidence for the involvement of alpha‐2 adrenoceptors in the sedative effect of detomidine, a novel sedative‐analgesic
Author(s) -
VIRTANEN R.,
RUSKOAHO H.,
NYMAN L.
Publication year - 1985
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1985.tb00921.x
Subject(s) - detomidine , sedative , xylazine , prazosin , pharmacology , yohimbine , flumazenil , sedation , chemistry , analgesic , righting reflex , anesthesia , medicine , receptor , antagonist , reflex , biochemistry , ketamine
Virtanen, R., Ruskoaho, H. & Nyman, L. Pharmacological evidence for the involvement of alpha‐2 adrenoceptors in the sedative effect of detomidine, a novel sedative‐analgesic. J. vet. Pharmacol. Therap. 8, 30–37. The sedative effect and mechanism of action of a novel imidazole derivative, detomidine, were studied in laboratory animals. Three methods were used to quantify drug‐induced sedation: (i) decrease in spontaneous activity of mice; (ii) increase in barbiturate induced anaesthesia lime in mice; (iii) loss of righting reflex in chicks. Clonidine and xylazine were included in the studies for comparison. The sedative potency of detomidine was shown to be approximately equal to that of clonidine and much higher than that of xylazine. In all tests, the sedative effect of detomidine was inhibited by antagonists of alpha‐2 adrenoceptors (yohimbine, rauwolscine and idazoxan) but not by alpha‐1 antagonists (prazosin, corynanthine). Furthermore, an ex vivo receptor binding study in the rat showed that detomidine‐induced decrease in spontaneous activity was significantly correlated to [ 3 Hc]onidine but not to [ 3 H]prazosin displacement in brain membranes. These results show that detomidine has potent sedative effects in mice, rats and chicks, and suggest that this action is mediated through stimulation of alpha‐2 adrenoceptors. Raima Virtanen, Fartnos Group Ltd, Research Centre, P.O. Box 425, SF‐20101 Turku 10, Finland.