Prejunctional adrenoceptor activity of N-0437: a relatively selective DA2 dopamine receptor agonist

Eur J Pharmacol. 1990 Mar 27;178(3):351-5. doi: 10.1016/0014-2999(90)90114-l.

Abstract

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 = 14 micrograms) 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 x 10(2) micrograms). However, pretreatment with rauwolscine i.a., a relatively selective alpha 2-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cats
  • Domperidone / pharmacology
  • Dopamine Agents / pharmacology*
  • Electric Stimulation
  • In Vitro Techniques
  • Muscle Contraction / drug effects
  • Naphthalenes / pharmacology*
  • Nictitating Membrane / drug effects
  • Receptors, Adrenergic / drug effects*
  • Receptors, Dopamine / drug effects*
  • Receptors, Dopamine D1
  • Stereoisomerism
  • Tetrahydronaphthalenes / antagonists & inhibitors
  • Tetrahydronaphthalenes / pharmacology*
  • Thiophenes / antagonists & inhibitors
  • Thiophenes / pharmacology*
  • Yohimbine / pharmacology

Substances

  • Dopamine Agents
  • Naphthalenes
  • Receptors, Adrenergic
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Tetrahydronaphthalenes
  • Thiophenes
  • Yohimbine
  • Domperidone
  • rotigotine