Chlorphentermine
A chlorinated phentermine analogue marketed as an appetite suppressant from the late 1950s. Unlike phentermine it has minimal central stimulant/euphoric action, acting largely as a serotonin releaser, which is why it was later implicated in the same drug-induced phospholipidosis and valvulopathy/pulmonary concerns as other serotonergic anorectics. Long withdrawn from most markets.
01 Overview
Chlorphentermine (4-chloro-alpha,alpha-dimethylphenethylamine) was one of a wave of amphetamine-derived anorectics introduced for short-term weight loss. It produces far less locomotor stimulation and abuse liability than phentermine or amphetamine, and was briefly promoted as a 'non-stimulant' appetite suppressant.
It is now of mainly historical and pharmacological interest. It is a classic inducer of cationic amphiphilic drug (CAD) phospholipidosis in laboratory studies, and its serotonin-releasing profile links it to the fenfluramine class of concerns. It has been withdrawn or is unavailable in most jurisdictions.
02 Mechanism
A substituted phenethylamine that releases and to a lesser extent blocks reuptake of serotonin and, weakly, catecholamines in hypothalamic satiety circuits, suppressing appetite with little psychostimulant effect.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Immediate-release | 25–75 mg/day | Oral | Divided doses were also used before sustained-release forms. |
| Typical anorectic dose | 65 mg/day | Oral | Historically one 65 mg sustained-release capsule each morning for short-term use. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Appetite suppressionReduced hunger and caloric intake over a few weeks of use, comparable to other anorectics of its era. | modest short-term weight loss | Clinical | |
| Low stimulationLittle of the wakefulness, euphoria or motor activation seen with phentermine, reflecting its serotonergic rather than dopaminergic action. | minimal | Clinical |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Drug-induced phospholipidosisA prototypical cationic amphiphilic drug that causes lamellar lipid accumulation in tissues in animal studies. | Moderate | Preclinical hallmark | Preclinical | |
| Dry mouth and insomniaAnticholinergic-like dryness and mild sleep disturbance typical of anorectics. | Mild | Common | Clinical |