Norfenfluramine

Norfenfluramine, also known as desmethylfenfluramine, is a metabolite of the anorectic drug fenfluramine. Fenfluramine itself was withdrawn from the market in many countries in the late 1990s due to concerns about its association with heart valve damage and pulmonary hypertension. Norfenfluramine is pharmacologically active and contributes to the effects of fenfluramine.

Norfenfluramine primarily acts as a serotonin releasing agent and reuptake inhibitor. This means it increases the levels of serotonin, a neurotransmitter associated with mood, appetite, and sleep, in the brain. By enhancing serotonergic activity, fenfluramine and its metabolite norfenfluramine can suppress appetite and promote a feeling of fullness.

The metabolic pathway involves the dealkylation of fenfluramine to produce norfenfluramine. This conversion occurs in the liver. While fenfluramine was prescribed for weight loss, the serious side effects led to its discontinuation. Research has continued into the mechanisms of action and potential long-term effects of these compounds. The cardiovascular risks, particularly valvulopathy, were a major driver for the withdrawal of fenfluramine-containing medications. Due to these risks, norfenfluramine itself is not used as a standalone medication.