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The binding of leu-enkephalin to synaptosome-enriched fractions prepared from rat whole brain has been measured in the presence and absence of haloperidol, chlorpromazine and chlozapine. All three neuroleptics produced a dose-dependent inhibition of the binding with inhibition constants of 33.7, 89.6, and 34.2 microM for haloperidol, chlorpromazine, and clozapine, respectively, and resulted in parabolic Hill plots suggestive of multiprocess modes of action rather than simple competitive or noncompetitive interactions. Except for the case of haloperidol, the inhibition constants are comparable to brain tissue levels of neuroleptics after chronic administration. This suggests that neuroleptic treatment may block a significant fraction of endogenous leu-enkephalin from reaching its CNS receptors.
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