Dopamine receptor sequences. Therapeutic levels of neuroleptics occupy D2 receptors, clozapine occupies D4.
Dopamine (DA) D2, D3, and D4 receptors are targets for antipsychotic drugs. The recent cloning, deoxyribonucleic acid sequencing, and brain location of these receptors provide new insight on the DA hypothesis of schizophrenia, particularly for the basis of antipsychotic therapy of schizophrenia. In schizophrenia brain tissue, D2 receptors are elevated and have lost the link to D1 receptors. Brain positron-emission tomography studies of patients may also reveal elevated D2, depending on the method used. Hallucinations and positive symptoms are blocked when about 70% of the D2 receptors are occupied by neuroleptic drugs. An analysis of the literature indicates that therapeutic concentrations of antipsychotic drugs (in the patient's cerebrospinal fluid or plasma water) act primarily at D2 receptors, with the exception of clozapine, which acts at D4 receptors.
Seeman
P
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Department of Pharmacology, University of Toronto, Canada.
D000595:Amino Acid Sequence; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D006801:Humans; D008969:Molecular Sequence Data; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D050638:Receptors, Dopamine D4
D014150:Antipsychotic Agents; C493599:DRD4 protein, human; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D003024:Clozapine