PREJUNCTIONAL ADRENOCEPTOR ACTIVITY OF N-0437 - A RELATIVELY SELECTIVE DA2 DOPAMINE RECEPTOR AGONIST

被引:7
作者
CROSSON, CE
BURKE, JA
CHAN, MF
POTTER, DE
机构
[1] BAYLOR UNIV,CTR BIOTECHNOL,4000 RES FOREST DR,WOODLANDS,TX 77381
[2] ALLERGAN PHARMACEUT INC,DISCOVERY RES,IRVINE,CA 92714
关键词
(Enantiomers); Aminotetralin; Dopamine DA[!sub]2[!/sub] receptor agonists; N-0437; Nictitating membrane (cat);
D O I
10.1016/0014-2999(90)90114-L
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Prejunctional adrenoceptor activity of N-0437, 2[N-n-propyl-N-2-(thienylethyl-amino)-5-hydroxytetralin], was investigated by means of the cat nictitating membrane (CNM) preparation. Intra-arterial (i.a.) administration of N-0437 produced a dose-related inhibition (ED50 = 14μg) of the CNM contractions elicited by electrical stimulation of pre- and postganglionic sympathetic nerves of the superior cervical ganglion. Pretreatment with domperidone i.a., a relatively selective DA2 receptor antagonist, markedly attenuated the CNM response to racemic N-0437 (ED50 = 6.7 × 102μg). However, pretreatment with rauwolscine i.a., a relatively selective α2-receptor antagonist, did not alter the CNM responses to racemic N-0437. Evaluation of the (R)-(+) and (S)-(-) enantiomers showed that only the (S)-(-) enantiomer was active in suppressing the contractions in the CNM preparation. These results demonstrate that N-0437 is a potent agonist for prejunctional DA2 dopamine receptors on peripheral sympathetic nerves in the CNM and that these peripheral DA2 receptors appear to be enantioselective. © 1990.
引用
收藏
页码:351 / 355
页数:5
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