Alpha 2-adrenoceptor blocking properties of the alpha 1-selective agonist 2-(2-chloro-5-trifluoromethylphenylimino)imidazolidine (St 587).

The selective alpha 1-adrenoceptor agonist 2-(2-chloro-5-trifluoromethylphenylimino)imidazolidine (St 587) was tested with respect to putative alpha 2-adrenoceptor blocking properties. In these studies 6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine (B-HT 920) was used as a selective alpha 2-adrenoceptor agonist. At peripheral presynaptic sites St 587 (1 mg/kg i.v.) significantly antagonized the inhibitory effect of B-HT 920 (3-30 micrograms/kg i.v.) on electrically induced tachycardia in pithed rats. To study influences on central sympathoinhibition, urethane anaesthetized, vagotomized rats were used. Parameter measured was heart rate and this was decreased by B-HT 920. St 587 antagonized this effect in the range 1-10 mg/kg s.c. in a dose-dependent manner. These vagotomized rats were pretreated with prazosin, thus a central stimulation of alpha 1-adrenoceptors by St 587 was excluded. In anaesthetized dogs with beta-adrenoceptors blocked 10 micrograms/kg B-HT 920 intracisternally promoted a vagally mediated reflex bradycardia as elicited by angiotensin. St 587 given 20 min later with 100 micrograms/kg intracisternally almost completely abolished this effect. In mice, the exploratory activity was greatly diminished by treatment with the alpha 2-adrenoceptor agonists B-HT 920 (200 micrograms/kg s.c.) or azepexole (20 mg/kg s.c.) and this effect was partly antagonized by St 587 (0.1 or 1 mg/kg i.p.). In behavioral experiments dogs treated with St 587 (0.3-10 mg/kg i.v.) showed signs of irritation, especially in higher doses. Dogs treated with B-HT 920 (0.3 mg/kg i.v.) fell into a narcotic state, dogs treated in addition with St 587 (0.3-3 mg/kg i.v.) remained conscious but were remarkably sedated.(ABSTRACT TRUNCATED AT 250 WORDS)