- 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. Half Life: 16 to 31 hours
- Uses/Sources: Used as an anorectic in the treatment of obesity.
- Health Effects: Using large amounts of these drugs can result in a condition known as amphetamine psychosis -- which can result in auditory, visual and tactile hallucinations, intense paranoia, irrational thoughts and beliefs, delusions, and mental confusion.
- Symptoms: 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.
- Route of Exposure: Readily absorbed from the gastro-intestinal tract and buccal mucosa.
- Carcinogenicity: No indication of carcinogenicity to humans (not listed by IARC).
- Toxicity: Adult monkeys have an LD<sub>50</sub> of 15 to 20 mg/kg, whereas for young monkeys the LD<sub>50</sub> is only 5 mg/kg. (A308)
Mechanism of Action
|Target Name||Mechanism of Action||References|
Sodium-dependent dopamine transporter
Sodium-dependent noradrenaline transporter
Amine oxidase [flavin-containing] A
|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.||