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Antipsychotic drugs

المؤلف:  Sue Jickells , Adam Negrusz (Editors)

المصدر:  Clarkes Analytical Forensic Toxicology

الجزء والصفحة:  P27-28

2026-09-14

59

Antipsychotic drugs

The first antipsychotic drugs were largely of the phenothiazine type represented by thioridazine and chlorpromazine. They undergo sulfoxidation to yield sulfoxides and sulfones. In addition, oxidation at the nitrogen, hydroxylation of one or both of the aromatic rings, N-dealkylation of the side-chain and fission of the side-chain may also occur. The phenolic metabolites are then conjugated with glucuronic acid or sulfate and excreted in both the urine and the bile. The number of different metabolic routes that are possible results in a complex mixture of metabolites for many phenothiazines. For example, many of the drugs that contain an N, N-dialkylaminoalkyl side-chain (e.g. chlorpromazine) are metabolised extensively by N-oxidation, together with hydroxylation, sulfoxidation and N-dealkylation. Thioridazine is oxidised predominantly on the side-chain sulfur to active sulfoxide and sulfone metabolites (Fig. 1).

Haloperidol is metabolised by side-chain oxidation to a propionic acid derivative (Fig. 2) which is then conjugated, or by reduction of the keto group. Clozapine is metabolised to the active desmethyl form (norclozapine), which is often measured with the parent drug in therapeutic drug monitoring situations. Olanzapine is metabolised by N-demethylation and oxidation to a 2-hydroxymethyl metabolite, and N-glucuronidation. Risperidone is metabolised to the pharmacologically active 9-hydroxy metabolite. Inactive 7-hydroxy and N-dealkyl metabolites are also produced.

Figure 1 Thioridazine metabolic pathways.

Figure 2 Haloperidol metabolic pathways.