Neuroleptics

Abstract

Neuroleptics are antipsychotic drugs that are used to treat schizophrenia and bipolar disorder. They are subdivided into “typical” and “atypical” drug classes, based on chemical structure and associated pharmacological properties. Typical neuroleptics include phenothiazines, thioxanthenes, butyrophenones, dihydroindoles, dibenzoxapines, diphenylbutylpiperidines, and benzamides. Atypical neuroleptics include clozapine, risperidone, ziprasidone, sertindole, and benzothiazepine derivatives. Typical neuroleptics are believed to have dopamine antagonism as their mechanism of action; clozapine and the other atypical antipsychotic drugs have a different mechanism of action that possibly involves dopamine receptors, the serotonin 5-HT2 receptors, or both. Neuroleptics are extensively metabolized by various cytochrome P450 isozymes. These drugs produce both neurologic and non-neurologic side effects; the most severe toxic effects are the extrapyramidal effects that include dystonia, tardive dyskinesia, and akathisia. Plasma concentrations of neuroleptic agents do not correlate well with clinical signs and symptoms. The chemistry, pharmacology, analysis, and interpretation of these drugs in forensic toxicology investigations are discussed.