Haloperidol increases the cerebrospinal fluid concentrations of cyclic GMP in schizophrenic patients.

The concentration of cyclic guanosine 3',5' monophosphate (cGMP) in cerebrospinal fluid (CSF) is supposed to reflect central cholinergic activity. Earlier findings in the literature of decreased CSF concentrations of cGMP in drug-free schizophrenic patients accorded with the hypothesis of a cholinergic-dopaminergic imbalance in schizophrenia, with a relative dominance of dopaminergic activity. In the present study, treatment with haloperidol for 3 weeks significantly increased the CSF concentration of cGMP in 14 of 18 schizophrenics. This finding suggests that haloperidol and possibly other antipsychotic drugs might restore the cholinergic-dopaminergic balance in schizophrenia through central cholinergic stimulation in addition to the blockade of dopaminergic receptors.