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Of the several dopamine-sensitive sites in the brain, the one that most correlates with psychomotor behaviour is the D2 receptor. This receptor has two states. The D2Hi state is characterized by its nM affinity for dopamine. The D2Lo state is typified by its microM affinity for dopamine. Neuroleptics have the same affinity (50 pM for spiperone) for both states. Guanine nucleotides convert most, if not all, of the D2Hi sites into D2Lo sites. Any D2Hi sites which are insensitive to GTP, if such exist, may be separate D4 sites. In addition to the binding of 3H-spiperone being higher in post-mortem schizophrenic brains, the proportions of the D2 receptor in the D2Hi state appear to be less in preliminary data on the schizophrenic brain.
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