Dopamine D4 receptors bind inactive (+)-aporphines, suggesting neuroleptic role. Sulpiride not stereoselective.
In order to identify new atypical antipsychotic drugs which are more selective for the human dopamine D4 receptor than for the human dopamine D2 (long) receptor, we tested enantiomer pairs of dopamine agonists and dopamine antagonists on the expressed proteins of these cloned receptors. The (+)-aporphines ((+)-N-propyl-norapomorphine, 11-OH-N-propyl-norapomorphine and (+)-apomorphine) bound to the dopamine D4 receptor with selectivities up to 20 times greater than to the dopamine D2 receptor, suggesting that these pharmacologically inactive enantiomers may succeed as atypical neuroleptics.
Seeman
P
P
Department of Pharmacology, University of Toronto, Canada.
Van Tol
H H
HH
D014150:Antipsychotic Agents / Q000378:metabolism*; D001060:Aporphines / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050638:Receptors, Dopamine D4; D013237:Stereoisomerism; D013469:Sulpiride / Q000378:metabolism*
D014150:Antipsychotic Agents; D001060:Aporphines; C493599:DRD4 protein, human; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D013469:Sulpiride