Microdialysis and striatal dopamine release: stereoselective actions of the enantiomers of N-0437.
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.
Timmerman
W
W
Department of Pharmacy, State University of Groningen, The Netherlands.
Westerink
B H
BH
De Vries
J B
JB
Tepper
P G
PG
Horn
A S
AS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013469:Sulpiride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D015259:Dopamine Agents; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D013876:Thiophenes; D015102:3,4-Dihydroxyphenylacetic Acid; D013469:Sulpiride; C047508:rotigotine; D007608:Kainic Acid; D004298:Dopamine