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)