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Effects of putative α‐adrenoceptor antagonists and of other compounds on the loss of the righting reflex and on exophthalmia induced by xylazine in the rat
Author(s) -
Colpaert F. C.
Publication year - 1986
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430070204
Subject(s) - yohimbine , xylazine , phentolamine , phenoxybenzamine , idazoxan , prazosin , pharmacology , partial agonist , guanabenz , chemistry , apomorphine , agonist , clonidine , endocrinology , nalorphine , tolazoline , lisuride , antagonist , (+) naloxone , medicine , stimulation , anesthesia , receptor , propranolol , ketamine , dopamine agonist
Intraperitoneal injection of 20 mg/kg of xylazine causes loss of the righting reflex (LRR) and exophthalmia in the rat. The experiments determined some of the pharmacological characteristics of these responses to xylazine. The putative α 2 ‐adrenoceptor antagonists yohimbine, piperoxan, CGS 7525 A, and idazoxan blocked the LRR response; tolazoline, phentolamine, and salbutamol attenuated the response to some extent, whereas prazosin, aceperone, and phenoxybenzamine exerted no apparent effect. The putative α 2 ‐agonists clonidine, guanabenz, guanfacine, guanoxabenz, tiamenidine, and naphazoline were identified in an earlier study as acting only as partial agonists in depressing rat behavior and were found here to antagonize partially the LRR response. Other compounds that attenuated but did not block the response either have some affinity for and perhaps act as partial antagonists at α 2 ‐receptors (e.g., phentolamine, LSD, lisuride) or exert some arousing or behaviorally stimulating action (e.g., cocaine, nomifensine, tranylcypromine, apomorphine). Arousing sensory stimulation also produced a partial attenuation of the LRR response. The xylazine‐induced exophthalmia appeared responsive to the putative α 1 ‐antagonists prazosin and aceperone, and other drugs exerting α 1 ‐antagonist activity also antagonized the exophthalmia. The doses at which compounds antagonize xylazine‐induced LRR and exophthalmia in rat might offer an estimate of the compounds' in vivo potency in acting as antagonists at a2‐ and a,‐adrenoceptors, respectively.