Kj Os Vi

PET has it been possible to determine the relative importance of these receptor subtypes in schizophrenic patients on neuroleptic therapy. Using PET the occupancy of D2 receptors in the cortical regions of the brains of schizophrenics treated with phenothiazines (chlorpromazine, trifluoper-azine or perphenazine), a thioxanthine (flupenthixol), butyrophenones (haloperidol or melperone), a diphenylbutylpiperazine (pimozide) or the atypical neuroleptics sulpiride, raclopride or clozapine has been calculated. The results of this study with this structurally disparate group of drugs showed that 65-89% of the D2 receptors were occupied. Other investigators have also shown that over 70% of D2 receptors are occupied in the brains of schizophrenics following effective treatment with melperone. In contrast, no D1 receptors were occupied by sulpiride or perphenazine, while 42% of these receptors were occupied by clozapine. From such a study it may be speculated that a D2 receptor antagonist action may be essential for the therapeutic effect of neuroleptics.

A summary of the new families of dopamine receptors and their distribution and properties is shown in Table 11.4.

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