This illustration depicts the normal operation of the dopaminergic terminal to the left, and the dopaminergic terminal in the presence of<unk>  to the right.<unk>  reverses the action of the dopamine transporter (DAT) by activating TAAR1 (not shown). TAAR1 activation also causes some of the dopamine transporters to move into the presynaptic neuron and cease transport (not shown). At VMAT2 (labeled VMAT),<unk>  causes dopamine efflux (release).|alt=An image of<unk>  pharmacodynamics Pharmacodynamics<unk>  has been identified as a potent full agonist of trace amine-associated receptor 1 (TAAR1), a G protein-coupled receptor (GPCR) that regulates brain catecholamine systems. Activation of TAAR1 increases cyclic adenosine monophosphate (cAMP) production and either completely inhibits or reverses the transport direction of the dopamine transporter (DAT), norepinephrine transporter (NET), and serotonin transporter (SERT). When<unk>  binds to TAAR1, it triggers transporter phosphorylation via protein kinase A (PKA) and protein kinase C (PKC) signaling, ultimately resulting in the internalization or reverse function of monoamine transporters.<unk>  is also known to increase intracellular calcium, an effect which is associated with DAT phosphorylation through a Ca2+/calmodulin-dependent protein kinase (CAMK)-dependent signaling pathway, in turn producing dopamine efflux. TAAR1 has been shown to reduce the firing rate of neurons through direct activation of G protein-coupled inwardly-rectifying potassium channels. TAAR1 activation by<unk>  in astrocytes appears to negatively modulate the membrane expression and function of EAAT2, a type of glutamate transporter. In addition to its effect on the plasma membrane monoamine transporters,<unk>  inhibits synaptic vesicle function by inhibiting VMAT2, which prevents monoamine uptake into the vesicles and promotes their release. This results in the outflow of monoamines from synaptic vesicles into the cytosol (intracellular fluid) of the presynaptic neuron, and their subsequent release into the synaptic cleft by the phosphorylated transporters. Other transporters that<unk>  is known to inhibit are SLC22A3 and SLC22A5. SLC22A3 is an extraneuronal monoamine transporter that is present in astrocytes, and SLC22A5 is a high-affinity carnitine transporter.<unk>  is also an agonist of the alpha-2 adrenergic receptors and sigma receptors with a greater affinity for σ1 than σ2, and inhibits monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). Sigma receptor activation by<unk>  may facilitate its central nervous system stimulant effects and promote neurotoxicity within the brain. Dextromethamphetamine is a stronger psychostimulant, but levomethamphetamine has stronger peripheral effects, a longer half-life, and longer perceived effects among addicts. At high doses, both enantiomers of<unk>  can induce similar stereotypy and<unk>  psychosis, but levomethamphetamine has shorter psychodynamic effects. Pharmacokinetics Following oral administration,<unk>  is well-absorbed into the bloodstream, with peak plasma<unk>  concentrations achieved in approximately 3.13–6.3 hours post ingestion.<unk>  is also well absorbed following inhalation and following intranasal administration. Due to the high lipophilicity of<unk> , it can readily move through the blood–brain barrier faster than other stimulants, where it is more resistant to degradation by monoamine oxidase. The<unk> etamine metabolite peaks at 10–24 hours.<unk>  is excreted by the kidneys, with the rate of excretion into the urine heavily influenced by urinary pH. When taken orally, 30–54% of the dose is excreted in urine as<unk>  and 10–23% as<unk> etamine. Following IV doses, about 45% is excreted as<unk>  and 7% as<unk> etamine. The half-life of<unk>  is variable with a range of 5–30 hours. CYP2D6, dopamine β-hydroxylase, flavin-containing monooxygenase 3, butyrate-CoA ligase, and glycine N-acyltransferase are the enzymes known to metabolize<unk>  or its metabolites in humans. The primary metabolites are<unk> etamine and 4-hydroxymethamphetamine; other minor metabolites include: , , , benzoic acid, hippuric acid, norephedrine, and phenylacetone, the metabolites of<unk> etamine. Among these metabolites, the active sympathomimetics are<unk> etamine, , , , and norephedrine.<unk>  is a CYP2D6 inhibitor. The main metabolic pathways involve aromatic para-hydroxylation, aliphatic alpha- and beta-hydroxylation, N-oxidation, N-dealkylation, and deamination. The known metabolic pathways include: Detection in biological fluids<unk>  and<unk> etamine are often measured in urine or blood as part of a drug test for sports, employment, poisoning diagnostics, and forensics. Chiral techniques may be employed to help distinguish the source of the drug to determine whether it was obtained illicitly or legally via prescription or prodrug. Chiral separation is needed to assess the possible contribution of levomethamphetamine, which is an active ingredients in some OTC nasal decongestants, toward a positive test result. Dietary zinc supplements can mask the presence of<unk>  and other drugs in urine.
Methamphetamine
Benzphetamine
Amphetamine
Benzyl alcohol
Benzocaine
Cannabis
Cannabis 
Nicotine