title: Prejunctional adrenoceptor activity of N-0437: a relatively selective DA2 dopamine receptor agonist.
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.
authors.affiliation: Discovery Research, Allergan Inc., Irvine, CA 92714.
authors.forename: C E
authors.initials: CE
authors.lastname: Crosson
authors.forename: J A
authors.initials: JA
authors.lastname: Burke
authors.forename: M F
authors.initials: MF
authors.lastname: Chan
authors.forename: D E
authors.initials: DE
authors.lastname: Potter
mesh_terms: D000818:Animals; D002415:Cats; D004294:Domperidone / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D009541:Nictitating Membrane / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D013237:Stereoisomerism; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D015259:Dopamine Agents; D009281:Naphthalenes; D011941:Receptors, Adrenergic; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D015016:Yohimbine; D004294:Domperidone; C047508:rotigotine