Top Gene Interactions
- Metabolism: Hepatic. The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine, with the main metabolites being amphetamine (active) and 4-hydroxymethamphetamine. Other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine. Route of Elimination: Excretion occurs primarily in the urine, the rate of which is dependent on urine pH. Between 30-54% of an oral dose is excreted in urine as unchanged methamphetamine and 10-23% as unchanged amphetamine. Following an intravenous dose, 45% is excreted as unchanged parent drug and 7% amphetamine. Half Life: The biological half-life has been reported in the range of 4 to 5 hours.
- Uses/Sources: For the treatment of Attention Deficit Disorder with Hyperactivity (ADHD) and exogenous 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: Manifestations of acute overdosage with methamphetamine include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning usually terminates in convulsions and coma.
- Treatment: Management of acute methamphetamine intoxication is largely symptomatic and includes gastric evacuation, administration of activated charcoal, and sedation. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendations in this regard. Acidification of urine increases methamphetamine excretion, but is believed to increase risk of acute renal failure if myoglobinuria is present. Intravenous phentolamine has been suggested for possible acute, severe hypertension, if this complicates methamphetamine overdosage. Usually a gradual drop in blood pressure will result when sufficient sedation has been achieved. Chlorpromazine has been reported to be useful in decreasing CNS stimulation and sympathomimetic effects. (L1712)
- Route of Exposure: Methamphetamine is rapidly absorbed from the gastrointestinal tract with peak methamphetamine concentrations occurring in 3.13 to 6.3 hours post ingestion. Methamphetamine is also well absorbed following inhalation and following intranasal administration. It is distributed to most parts of the body. Because methamphetamine has a high lipophilicity it is distributed across the blood brain barrier and crosses the placenta.
Mechanism of Action
|Target Name||Mechanism of Action||References|
Sodium-dependent serotonin transporter
Alpha-2A adrenergic receptor
Sodium-dependent dopamine transporter
Trace amine-associated receptor 1
Sodium-dependent noradrenaline transporter
Amine oxidase [flavin-containing] A
Amine oxidase [flavin-containing] B
Synaptic vesicular amine transporter
Sigma non-opioid intracellular receptor 1
Alpha-2B adrenergic receptor
Alpha-2C adrenergic receptor
Chromaffin granule amine transporter
Alpha-1A adrenergic receptor
Alpha-1B adrenergic receptor
|Methamphetamine enters the brain and triggers a cascading release of norepinephrine, dopamine and serotonin. To a lesser extent methamphetamine acts as a dopaminergic and adrenergic reuptake inhibitor and in high concentrations as a monamine oxidase inhibitor (MAOI). The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown.||