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Fluphenazine is a high-potency typical antipsychotic that primarily acts as a dopamine D2 receptor antagonist in the mesolimbic pathway, reducing positive symptoms of schizophrenia. Extrapyramidal symptoms (EPS), such as dystonia, akathisia, and parkinsonism, are common due to potent D2 blockade in the nigrostriatal pathway. Neuroleptic malignant syndrome (NMS), though rare, is a life-threatening adverse effect characterized by rigidity, hyperthermia, altered mental status, and autonomic instability. CYP2D6 inhibitors (e.g., fluoxetine, paroxetine) can increase fluphenazine plasma concentrations, potentially raising the risk of toxicity and side effects. Concomitant use of fluphenazine with CNS depressants (e.g., alcohol, benzodiazepines) can enhance sedation and respiratory depression.

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