The Sound of Evolution
Methamphetamine
Mechanism of action:
Methamphetamine is a central nervous system stimulant and a phenethylamine derivative. Structurally, it is similar to amphetamine, but due to its higher lipid solubility, it crosses the blood-brain barrier more easily. Methamphetamine enters presynaptic neurons through the dopamine transporter, norepinephrine transporter, and serotonin transporter. It inhibits VMAT2 (vesicular monoamine transporter 2), preventing dopamine and other monoamines from being properly stored in synaptic vesicles and causing large amounts of neurotransmitters to accumulate in the cytoplasm. The accumulated dopamine, norepinephrine, and serotonin are then released into the synaptic cleft through reverse transport via their respective transporters, causing a sharp increase in synaptic neurotransmitter concentrations and intensifying neuronal stimulation.
Reference(s):
1. Schepers RJ et al. (2003). Methamphetamine and amphetamine pharmacokinetics in oral fluid and plasma after controlled oral methamphetamine administration to human volunteers. Clin Chem.
2. McGregor C et al. (2005). The nature, time course and severity of methamphetamine withdrawal. Addiction.
3. Bennett BA et al. (1998). Methamphetamine-induced alterations in dopamine transporter function. Brain Res.