Phenothiazines

Phenothiazines were introduced originally to treat psychotic states, including mania and schizophrenia. Subsequently, many were found to have useful antiemetic properties and are now used routinely during cancer chemoradiotherapy. The main mechanism of action of the phenothiazines is antagonism of D2 receptors, but some of their clinical effects may arise from blockade of other relevant neurotransmiers.
Prochlorperazine is used routinely in the treatment of PONV and labyrinthine disorders. It can be administered via intramuscular, oral or buccal routes. A dverse effects include sedation, hypotension and extrapyramidal features.
Perphenazine is not licensed for treatment of PONV in the UK but has proved to be useful as an oral antiemetic preparation.

Phenothiazines are classified on the basis of their chemistry, pharmacological actions, and potency. Chemical classifications include the aliphatic (e.g., chlorpromazine; Thorazine), piperidine (e.g., thioridazine; Mellaril), and piperazine subfamilies. The piperazine derivatives are generally more potent and pharmacologically selective than the others. The thioxanthenes (e.g., thiothixene; Navane) are chemically related to the phenothiazines and have nearly equivalent potency. The butyrophenone haloperidol (Haldol) is structurally distinct from the two preceding groups, offering greater potency and fewer autonomic side effects.The dibenzodiazepine clozapine (Clozaril) bears some structural resemblance to the phenothiazine group but causes little extrapyramidal toxicity. The benzisoxazole risperidone (Risperdal) is representative of many of the newer agents in having a unique structure relative to the older groups while retaining antipsychotic potency and a better side effect profile.