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.