Substituted 3-phenylpiperidines: new centrally acting dopamine autoreceptor antagonists.
The (+)-and (-)-enantiomer of compounds 4 and 5 were synthesized and tested for central dopamine (DA) receptor stimulating activity, using biochemical and behavioral tests in rats. Based on the available data the (-)-enantiomers of 4 and 5 are characterized as centrally acting DA autoreceptor antagonists with oral activity. They display a similar pharmacological profile as the prototype DA autoreceptor antagonists (+)-1 and (+)-2 and show a certain preference for the D3 DA receptor antagonist binding site.
Sonesson
C
C
Department of Pharmacology, University of Göteborg, Sweden.
Waters
N
N
Svensson
K
K
Carlsson
A
A
Smith
M W
MW
Piercey
M F
MF
Meier
E
E
Wikström
H
H
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001682:Biological Availability; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism; D018492:Dopamine Antagonists; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D018492:Dopamine Antagonists; D010880:Piperidines; D011954:Receptors, Dopamine; D004298:Dopamine