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Active ingredient: Phenmetrazine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Appetite Depressants
  • Central Nervous System Agents
  • Sympathomimetics

Dosage Forms

  • Tablet

Brands / Synonyms

2-Phenyl-3-Methylmorpholine; 3-Methyl-2-phenylmorpholine; Bromadryl; Cafilon; Dexphenmetrazine; Fenmetrazin; Fenmetrazina [INN-Spanish]; Marsin; Mefolin; Neo-zine; Oxazimedrine; Phenmetraline hydrochloride; Phenmetrazin; Phenmetrazine hydrochloride; Phenmetrazinum [INN-Latin]; Preludin; Preludin hydrochloride; Probese-P; Probese-P hydrochloride; Psychamine A 66; Psychamine A 66 hydrochloride; USAF Ge-1

Indications

Used as an anorectic in the treatment of obesity.

Pharmacology

Phenmetrazine is a sympathomimetic drug used primarily as an appetite depressant. Its actions and mechanisms are similar to dextroamphetamine. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. Phenmetrazine was originally sold under the tradename Preludin as an anorectic. It has since been removed from the market. It is by some considered to have a greater potential for addiction than the amphetamines, and has been abused in many countries, for example Sweden.

Mechanism of Action

Phenmetrazine is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron leading to an increase in the release of these monoamines into the extraneuronal space. Dopamine integrates incoming sensory stimuli, initiates and controls fine movement (nigro-neostriatal pathway), controls emotional behavior (midbrain mesolimbic-forebrain system) and controls hypothalamic-pituitary endocrine system (tubero-infundibular system). It is this latter effect on the tubero-infundibular systm that seems to lead to reduced food intake. Phenmetrazine also acts as a monoamine oxidase inhibitor.

Absorption

Readily absorbed from the gastro-intestinal tract and buccal mucosa.

Toxicity

Adult monkeys have an LD50 of 15 to 20 mg/kg, whereas for young monkeys the LD50 is only 5 mg/kg. Symptoms of overdose include acute central nervous system stimulation, cardiotoxicity causing tachycardia, arrhythmias, hypertension, and cardiovascular collapse. Whilst some patients show signs of toxicity at blood concentrations of 20 µg/L, chronic abusers of amphetamine have been known to have blood concentration of up to 3000 µg/L.

Biotrnasformation / Drug Metabolism

Primarily hepatic (via CYP3A and CYP2D6). Resistant to metabolism by monoamine oxidase. Metabolism involves deamination to para-hydroxyamphetamine and phenylacetone; this latter compound is subsequently oxidize to benzoic acid and excreted as glucuronide or glycine (hippuric acid) conjugate. Smaller amounts of amphetamine are converted to norephedrine by oxidation.

Contraindications

Anorexia, insomnia, psychopathic personality disorders, suicidal tendencies, Gilles de la Tourette syndrome and other disorders, hyperthyroidism, narrow angle glaucoma, diabetes mellitis and cardiovascular diseases such as angina, hypertension and arrythmias (Dollery, 1991; Reynolds, 1996).

Drug Interactions

Acetazolamide - administration may increase serum concentration of phenmetrazine.
Alcohol - may increase serum concentration of phenmetrazine.
Ascorbic acid -lowering urinary pH, may enhance phenmetrazine excretion.
Furazolidone - phenmetrazine may induce a hypertensive response in patients taking furazolidone.
Guanethidine - phenmetrazine inhibits the antihypertensive response to guanethidine.
Haloperidol - limited evidence indicates that haloperidol may inhibit the effects of phenmetrazine but the clinical importance of this interaction is not established.
Lithium carbonate - isolated case reports indicate that lithium may inhibit the effects of phenmetrazine.
Monoamine oxidase inhibitor - severe hypertensive reactions have followed the administration of phenmetrazine to patients taking monoamine oxidase inhibitors.
Noradrenaline - phenmetrazine abuse may enhance the pressor response to noradrenaline.
Phenothiazines - phenmetrazine may inhibit the antipsychotic effect of phenothiazines, and phenothiazines may inhibit the anorectic effect of phenmetrazine.
Sodium bicarbonate - large doses of sodium bicarbonate inhibit the elimination of phenmetrazine, thus increasing the phenmetrazine effect.
Tobacco smoking - phenmetrazine appears to induce dose-related increases in cigarette smoking.
Tricyclic antidepressants - theoretically increases the effect of phenmetrazine, but clinical evidence is lacking.

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