This review addresses two questions. First, why does @entity1088 apparently occupy low levels of @entity935 D2 receptors in @entity1 , in contrast to all other antipsychotic drugs which occupy 70-80% of brain @entity935 D2 receptors? Second, what is the receptor basis of action of antipsychotic drugs which elicit low levels of @entity304 ? Antipsychotic doses of @entity1088 occupy between 0% and 50% of D2 receptors, as measured in @entity1 by a variety of radioligands. It has recently been found, however, that the percent occupancy of a receptor by a drug depends on the radioligand used to measure that receptor. Based on this new finding, this review concludes that @entity1088 clinically occupies high levels of D2 receptors in the absence of any radioligand. This occupancy is estimated to be of the order of 70-80% in the @entity935 -rich region of the @entity1 striatum, and even higher in the limbic D2-containing regions which are low in endogenous synaptic @entity935 . This conclusion arises from two different approaches. One approach is to relate the reported @entity1088 occupancies in the @entity1 striatum with the dissociation constants of the various radioligands at the D2 receptor. This relation extrapolates to approximately 70-80% occupancy by @entity1088 when @entity1088 competes with endogenous @entity935 at the D2 receptor. The second approach is to calculate the D2 occupancy of each antipsychotic drug, using the average spinal fluid concentration and the correct dissociation constant of the antipsychotic, thereby revealing that all antipsychotic drugs, including @entity1088 , occupy approximately 70-80% of @entity935 D2 receptors in the @entity1 striatum, and possibly higher in the limbic regions. As determined by the new dissociation constants, antipsychotic drugs which elicit @entity304 ( @entity6105 , @entity2644 , @entity11641 , @entity1767 , @entity1768 , @entity1090 ) bind more tightly than @entity935 to D2, while those antipsychotic drugs which elicit little or no @entity304 ( @entity58904 , @entity1089 , @entity69390 , @entity1088 , @entity20129 , @entity16680 , @entity3216 , @entity1037 , @entity22521 ) bind more loosely than @entity935 to D2 receptors. Compared to the tightly bound antipsychotic drugs, the more loosely bound antipsychotics generally require higher clinical doses, require fewer days for clinical adjustment, but may dissociate from the D2 receptor more rapidly and could lead to clinical relapse somewhat earlier than that found with the traditional tightly bound antipsychotic drugs.

Antipsychotic drugs which elicit little or no @entity304 bind more loosely than XXXX to brain D2 receptors, yet occupy high levels of these receptors.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity1088 :: ('MESH:D003024', 'Chemical') :: ['clozapine'] @entity1037 :: ('MESH:C076029', 'Chemical') :: ['olanzapine'] @entity304 :: ('MESH:D010302', 'Disease') :: ['Parkinsonism'] @entity16680 :: ('MESH:D008972', 'Chemical') :: ['molindone'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity22521 :: ('MESH:C066304', 'Chemical') :: ['sertindole'] @entity6105 :: ('MESH:D014268', 'Chemical') :: ['trifluperazine'] @entity3216 :: ('MESH:D013469', 'Chemical') :: ['sulpiride'] @entity2644 :: ('MESH:D002746', 'Chemical') :: ['chlorpromazine'] @entity69390 :: ('MESH:C003910', 'Chemical') :: ['perlapine'] @entity1768 :: ('MESH:D005476', 'Chemical') :: ['fluphenazine'] @entity1767 :: ('MESH:D006220', 'Chemical') :: ['haloperidol'] @entity20129 :: ('MESH:D017330', 'Chemical') :: ['remoxipride'] @entity58904 :: ('MESH:C008522', 'Chemical') :: ['melperone'] @entity1089 :: ('MESH:C069541', 'Chemical') :: ['seroquel'] @entity11641 :: ('MESH:D020891', 'Chemical') :: ['raclopride'] @entity1090 :: ('MESH:D018967', 'Chemical') :: ['risperidone']
@entity935 :: (MESH:D004298,Chemical) :: ['dopamine']
