(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0923), a selective D2 dopamine receptor agonist demonstrates the presence of D2 dopamine receptors in the mouse vas deferens but not in the rat vas deferens

PL Martin, M Kelly and NJ Cusack

Department of Pharmacology, Whitby Research, Inc., Richmond, Virginia.

Experiments were carried out using the D2 dopamine receptor-selective agonist (-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N- 0923) in the rat and the mouse isolated vas deferens to determine whether these tissues contained inhibitory D2 receptors in addition to their inhibitory alpha-2 adrenoceptors. In the mouse vas deferens N- 0923 and the alpha-2 adrenoceptor agonist clonidine inhibited the electrically evoked twitch responses. The actions of clonidine, but not of N-0923, were antagonized by the alpha-2 antagonist idazoxan (pKb = 7.9), and responses to N-0923 were antagonized by the D2 antagonist sulpiride (pKb = 8.1). In the rat vas deferens, clonidine, but not N- 0923, inhibited the twitch responses and these inhibitions were antagonized by idazoxan (pKb = 7.9) but not by sulpiride. Other D2 receptor agonists were tested in the mouse and in the rat vas deferens for their ability to activate D2 and alpha-2 receptors, respectively. At the D2 receptors in the mouse vas deferens (alpha-2 blocked) the potency order was (+)-propyl-9-hydroxy-naphtoxazine > pergolide > N- 0923 = apomorphine > bromocriptine > quinpirole > dopamine. At the alpha-2 receptors in the rat vas deferens the potency order was pergolide > bromocriptine > (+)-propyl-9-hydroxynapthoxazine > apomorphine > quinpirole > or = dopamine. N-0923 was inactive but antagonized the responses to clonidine. N-0923 was therefore the most D2 receptor selective agonist tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 267, Issue 3, pp. 1342-1348, 12/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics