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Maximal magnitude of effect and potency of putative α‐adrenoceptor agonists in causing CNS depression, in relaxing muscle, and in lowering body temperature in rat
Author(s) -
Colpaert Francis 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.430070303
Subject(s) - methoxamine , clonidine , xylazine , guanabenz , yohimbine , phenylephrine , medicine , endocrinology , hypothermia , potency , agonist , chemistry , oxymetazoline , reflex , anesthesia , antagonist , receptor , ketamine , blood pressure , biochemistry , in vitro
Abstract This study determined the maximal magnitude of effect and the potency of 20 putative α‐adrenoceptor agonists in causing CNS depression, muscle relaxation, and hypothermia in rat; CNS depression was evaluated by the degree to which the righting reflex was impaired. The compounds being examined were xylazine, UK‐14,304, oxymetazoline, ergotamine, phenylephrine, l‐adrenaline, guanabenz, l‐noradrenaline, B‐HT 920, dopamine, guanfacine, guanoxabenz, isoproterenol, naphazoline, tramazoline, tiamenidine, clonidine, azepexole, St‐587, and methoxamine. Observations were carried out 15, 30, and 60 min after i.p. injection of doses that covered the dynamic range of the compounds' apparent activity. The putative α 2 ‐adrenoceptor agonists xylazine and UK‐14,304 ranked highest in terms of the magnitude of behaviorally depressant activity and also ranked high in relaxing muscle and lowering body temperature. The magnitude of effect of xylazine and UK‐14,304 on the behavioral response, on muscle tone, and on body temperature exceeded that of all putative α 1 ‐adrenoceptor agonists tested, including phenylephrine, St‐587, and methoxamine. Clonidine ranked last in terms of the magnitude of its effects on the behavioral response and on muscle tone and ranked fifth in terms of its maximal hypothermic activity. The data characterize xylazine and UK‐14,304 as full agonists and clonidine as a particu‐larly weak agonist in depressing rat behavior; other compounds exerted intermediate magnitudes of activity.