Mechanisms of action of anti-psychotic drugs.

Anti-psychotic drugs The anti-psychotic drugs, e.g. haloperidol and chlorpromazine, comprise a large group of drugs that are used to treat the symptoms of schizophrenia [ l ] . The principal therapeutic effect of the drugs is on the positive (psychotic) symptoms of the disorder, although some drugs, e.g. clozapine, are claimed to have effects on the negative symptoms. After the discovery of dopamine as a neurotransmitter in the brain it was shown that the anti-psychotic drugs were interfering somehow with the actions of dopamine in the brain; on the basis of behavioural studies, this seemed to be via a blockade of dopamine receptors. With the advent of assays for the different dopamine receptor subtypes (stimulation of adenylate cyclase for D1-like receptors and ligand binding assays for DZlike receptors; details of nomenclature of dopamine receptors are in [2,3]) it became clear that there was an excellent correlation between the daily dose of a range of drugs used to treat schizophrenia and the affinities of these drugs for the D2-like receptors. Thus it was concluded that the drugs were acting at DZ-like dopamine receptors. After the discovery of the different dopamine receptor subtypes by using molecular biological techniques, these D2-like effects could be at D2, D3 or D4 receptors [2]. A consideration of the affinities of the anti-psychotic drugs for these dopamine receptors shows that some anti-psychotic drugs have a high affinity for the D2 and D3 receptors but a rather low affinity for the D4 receptor [3]. This suggests that occupancy of D2 and D3 receptors might contribute to the antipsychotic effects but occupancy of D4 receptors is not mandatory for achieving an anti-psychotic effect.