Dopaminomimetic psychosis in Parkinson's disease patients - Diagnosis and treatment

Dopaminomimetic agents; which were rationally designed to reverse dopamine deficits in the substantia nigra and ventral tegmental area of the parkinso nian midbrain, effectively attenuate deficits in motor and non-motor behavi or thought to be elicited by dopamine deficiencies in the striatal and fron tal limbic regions, respectively. On the other hand, dopaminomimetic medica tions may also in:duce perturbations in postsynaptic peptides, causing dopa minergic hypersensitivity. Drug-induced chronic dopaminomimetic psychosis a fflicts about one-fifth of PD patients on dopaminergic regimens. Although t he long-held mechanism for psychosis in PD is excessive stimulation of meso corticolimbic dopamine receptors, interactions between dopamine and seroton in, as well as participation of serotonin-modulated GABAergic neurons may a lso contribute to the pathophysiology. Reduction or withdrawal of anticholi nergic agents, amantadine, and dopamine precursors or agonists constitutes a first approach to the problem but is often insufficient. Unfortunately, t ypical antipsychotic agents such as haloperidol, which selectively antagoni zes dopamine D-2 receptors, can induce extrapyramidal syndromes such as tar dive parkinsonism. On the other hand, emerging atypical neuroleptics such a s clozapine, quetiapine, and olanzapine, which antagonize 5HT-2A receptors (among others), inhibit D-2 receptors to a lesser degree and exhibit select ive binding to mesolimbic (vs. striatal) dopamine receptors. The limbic sel ectivity of these agents appears to be of greater magnitude than that typic al of risperidone. in addition, the selective antiserotonergic agent ondans etron is a prospective therapeutic option. The pharmacologic properties of these agents are explored.