DOPAMINE-RECEPTOR BINDING OF UOROPHENYL)-4-OXOBUTYL]-1,2,3,6-TETRAHYDROPYRIDINE (HPTP), AN INTERMEDIATE METABOLITE OF HALOPERIDOL

The neuroleptic agent haloperidol (HP) is biotransformed to metabolite s such as uorophenyl)-4-oxobutyl]-1,2,3,6-tetrahydropyridine (HPTP) an d henyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]pyridinium (HPP+). In this s tudy, radioligand binding studies were performed using [H-3]SCH23390 a s a dopamine D1 receptor ligand and [H-3]spiperone as a D2 ligand. K-i values for D1 receptors were 35.8 mu M and 54.9 mu M for HP and HPTP, respectively. Corresponding values for D2 receptors were 39.1 nM and 329.8 nM. These results indicate similar low affinities in the micromo lar range for both HP and HPTP at the dopamine D1 receptor, a much hig her affinity of both HP and HPTP for the D2 receptor than for the D1 r eceptor, and that HPTP binds to D2 receptors with a 9-fold lower affin ity than HP. The data are consistent with observations in mice that HP TP is a much less potent acute neuroleptic agent than HP.