Possible function of alpha 1-adrenoceptors in the CNS in anaesthetized and conscious animals.
The influence of St 587 (2-(2-chloro-5-trifluoromethylphenylimino)imidazolidine), a selective alpha 1-adrenoceptor agonist which easily penetrates the blood-brain barrier, was tested on behavior and cardiovascular functions, respectively. The substance (up to 10 mg/kg subcutaneously (s.c.)) did not increase the exploratory activity of naive mice. The hexobarbitone 'sleeping' time in mice was reduced in a dose-dependent manner (St 587 ED50 = 14.4 mg/kg s.c.). Haloperidol 10 mg/kg s.c. induced catalepsy which was antagonized by St 587 in a dose-dependent manner (ED50 = 2.7 mg/kg i.p.). Conversely, the alpha 1-adrenoceptor-blocking agents prazosin and corynanthine elicited catalepsy in mice which had been treated with a subthreshold dose (2 mg/kg s.c.) of haloperidol; the ED50 values of the antagonists were 0.26 and 4.7 mg/kg i.p., respectively. In anaesthetized cats blood pressure and heart rate were not affected by 100 micrograms/kg St 587 injected into the left vertebral artery. In conscious dogs with beta-adrenoceptors blocked, the drug was without effect (100 micrograms/kg intracisternally) on vagally mediated reflex bradycardia, as evoked by intravenous noradrenaline injection. As a positive control the alpha 2-adrenoceptor agonist B-HT 920 which is equipotent to St 587 with respect to peripheral vasopressor effects in rats was injected with 10 micrograms/kg intracisternally and facilitated the reflex bradycardia. It is concluded that alpha 1-adrenoceptors within the brain mediate behavioral activation in states of CNS depression but remain without effect on cardiovascular centers.
Pichler
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L
Kobinger
W
W
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D002375:Catalepsy / Q000139:chemically induced; D002415:Cats; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006591:Hexobarbital / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011311:Pressoreceptors / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D012018:Reflex / Q000187:drug effects; D012890:Sleep / Q000187:drug effects
D011942:Receptors, Adrenergic, alpha; C030655:St 587; D006591:Hexobarbital; D006220:Haloperidol; D003000:Clonidine