Microdialysis and striatal dopamine release: stereoselective actions of the enantiomers of N-0437

Eur J Pharmacol. 1989 Mar 14;162(1):143-50. doi: 10.1016/0014-2999(89)90614-6.

Abstract

An intracerebral dialysis method was used to test both enantiomers of the very potent and selective dopamine (DA) D-2 agonist 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin, N-0437, for their actions on DA receptors in the striatum of the rat. (-)N-0437 induced a 60% decrease in DA release, which was independent of the presence or absence of a kainic acid lesion placed unilaterally in the striatum. Stereotyped behaviour was apparent following administration of the (-) enantiomer. Thus, (-)N-0437 displayed an agonistic action on both pre- and postsynaptic D-2 receptors. (+)N-0437 did not induce any effect in the release model after peripheral administration nor did it induce any form of stereotypy. A comparison between the effects of (-)N-0437 after oral (10 mumol/kg) and transdermal (10 mumol/kg) administration showed the advantages of the latter mode of administration. Transdermal application induced a much longer duration of action of the drug (13 h) in comparison with the oral mode (5 h). Thus, transdermal administration may be a very useful method of drug application for therapeutic use.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Administration, Cutaneous
  • Administration, Oral
  • Animals
  • Brain Chemistry / drug effects
  • Corpus Striatum / metabolism*
  • Dialysis
  • Dopamine / metabolism*
  • Dopamine Agents / pharmacology*
  • Injections, Intraperitoneal
  • Kainic Acid / pharmacology
  • Male
  • Naphthalenes / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Stereoisomerism
  • Sulpiride / pharmacology
  • Tetrahydronaphthalenes / pharmacology*
  • Thiophenes / pharmacology*

Substances

  • Dopamine Agents
  • Naphthalenes
  • Tetrahydronaphthalenes
  • Thiophenes
  • 3,4-Dihydroxyphenylacetic Acid
  • Sulpiride
  • rotigotine
  • Kainic Acid
  • Dopamine