Antipsychotic Agents and Dopamine Agonists

A large body of indirect but compelling pharmacological data implies the existence of dopaminergic defects in the brains of patients suffering from schizophrenic psychosis. Direct demonstration of a causative biochemical lesion in this disorder is still almost completely lacking and other neurohumoral systems may be involved. However, the Dopamine (DA) hypothesis has provided fertile soil, from which much of the recent progress in the understanding and treatment of schizophrenia and other diseases of the CNS have grown. Several groups have begun to examine the changes in DA receptors in various pathological states or in experimental models of them. For example, rats may be treated chronically with neuroleptic drugs to produce a model of tardive dyskinesia. In such animals, it is found that there is an increase in the total number of DA receptors in the basal ganglia. A very important observation has been made with respect to the state of DA receptors in the basal eanglia, and elsewhere in the brains of patients with schizophrenia. It is found that in the postmortem samples of brains from such patients there are an increased number of receptors for haloperidol binding in the putamen, caudate nucleus, and nucleus accumbens, but not in the frontal cortex. This provocative observation suggests that an increased number of DA receptors could be the biochemical defect responsible for the symptoms of schizophrenia.