Fluphenazine is a high-potency, first-generation antipsychotic medication. It’s part of the phenothiazine class of drugs and is used to treat chronic psychotic disorders, particularly schizophrenia. It is available in various forms, including oral tablets, oral liquid, and long-acting injectable formulations, which are often used for patients who have trouble adhering to their daily medication schedule.

Indication

The primary indication for fluphenazine is the management of psychotic disorders, most notably schizophrenia. It is effective in managing the “positive symptoms” of schizophrenia, which are symptoms that are added to a person’s life, such as:

• Hallucinations (seeing or hearing things that aren’t there)
• Delusions (firmly held false beliefs)
• Disorganized thought and speech

It may also be used off-label for other conditions like chronic tic disorders and Huntington’s disease to control abnormal movements.

Mechanism of Action

Fluphenazine’s primary mechanism of action is the antagonism of postsynaptic dopamine D2 receptors in the brain.

Dopamine Overactivity: Psychotic disorders like schizophrenia are associated with an overactivity of the dopamine system in certain brain regions, specifically the mesolimbic pathway. This excess dopamine signaling is thought to contribute to the positive symptoms of psychosis.

Receptor Blockade: By blocking the D2 receptors, fluphenazine reduces the effect of dopamine in these areas, thereby helping to control psychotic symptoms.

Other Receptor Interactions: Fluphenazine also has antagonistic effects on other receptors, including alpha-1 adrenergic receptors, muscarinic-1 receptors, and histamine-1 receptors. These additional actions contribute to both its therapeutic effects and its side effect profile, which can include sedation, dry mouth, and low blood pressure.