Dopamine D3 receptor binding by D3 agonist 7-OH-DPAT (7-hydroxy-dipropylaminotetralin) and antipsychotic drugs measured ex vivo by quantitative autoradiography

Because the dopamine D-3 receptor is primarily expressed in regions of the limbic system of brain, it was proposed that it may represent a target for antipsychotic drugs that is free of extrapyramidal side effects. An ex vivo receptor binding technique employing [H-3]7-OH-DPAT was used to evaluate in vivo occupancy of dopamine D-3 receptors in the rat nucleus accumbens by selective D-3 agonist 7-OH-DPAT (7-hydroxy-dipropylaminotetralin) and various antipsychotic drugs. With an ID50 value of 0.07 mg/kg, the selective D-3 agonist (+)-7-OH-DPAT had the most potent inhibitory effect on ex vivo binding of [H-3]7-OH-DPAT among all drugs tested. Clinical doses of phenothiazine drugs, such as chlorpromazine and levomepromazine, induce binding to D-3 receptors in vivo, while atypical antipsychotic drugs, such as clozapine, pimozide, and sulpiride, are very weak in inhibiting ex vivo binding of [H-3]7-OH-DPAT, indicating that the role of D-3 receptors as targets of antipsychotic drugs free of extapyramidal side effects may not be important.