Chapter 6. Antipsychotics

Publisher Summary Antipsychotic drugs are not only used for the treatment of schizophrenia, but they also have limited applications in mania, schizoaffective disorder, anxiety, dementia, and drug overdose. Although available antipsychotic drugs reduce delusions and hallucinations, symptoms of schizophrenia—such as poverty of speech and social withdrawal—are less improved. In addition, some patients obtain a little benefit from these drugs and relapse occurs frequently. Available antipsychotics also produce serious neurological side effects, including extra-pyramidal syndrome (EPS) and tardive dyskinesia. These limitations have stimulated efforts to identify new drugs with improved therapeutic profiles. The history, clinical use, and pharmacokinetics of antipsychotics, as well as the biological findings on DA receptor clones and the etiology of schizophrenia, are described in this chapter. The chapter discusses dopamine (DA) D2 receptor antagonists, multiple receptor antagonists, serotonergic agents, DA autoreceptor agonists, sigma ligands, and the properties of some miscellaneous compounds. Psychotic patients who respond to DA antagonist therapy show predrug evidence of elevated brain catecholamine release. A correlation was found between negative schizophrenic symptoms and apparent brain norepinephrine release in unmedicated schizophrenic patients who relapsed. Several theories have focused on the role of brain glutamate in antipsychotic drug action and in the etiology of schizophrenia.