Pharmacodynamics<unk>  is a<unk> ective inhibitor of MAO-B, irreversibly inhibiting it by binding to it covalently. It exerts effects by blocking the breakdown of dopamine, thus increasing its activity. Its possible neuroprotective properties may be due to protecting nearby neurons from the free oxygen radicals that are released by MAO-B activity. At higher doses,<unk>  loses its<unk> ectivity for MAO-B and inhibits MAO-A as well.<unk>  also inhibits CYP2A6 and can increase the effects of nicotine as a result.<unk>  also appears to activate σ1 receptors, having a relatively high affinity for these receptors of approximately 400 nM. Pharmacokinetics<unk>  has an oral bioavailability of about 10%, which increases when ingested together with a fatty meal, as the molecule is fat soluble.<unk>  and its metabolites bind extensively to plasma proteins (at a rate of 94%). They cross the blood–brain barrier and enter the brain, where they most concentrated at the thalamus, basal ganglia, midbrain, and cingulate gyrus.<unk>  is mostly metabolized in the intestines and liver; it and its metabolites are excreted in the urine. Buccal administration of<unk>  results in 5-fold higher bioavailability, more reproducible blood concentration, and produces less amphetamine metabolites than the oral tablet form. Metabolism<unk>  is metabolized by cytochrome P450 to L-desmethylselegiline and levomethamphetamine. Desmethylselegiline has some activity against MAO-B, but much less than that of<unk> . It is thought to be further metabolized by CYP2C19. Levomethamphetamine (the less potent of the two enantiomers of methamphetamine) is converted to levoamphetamine (the less potent of the two enantiomers of amphetamine, with regards to psychological effects). Due to the presence of these metabolites, people taking<unk>  may test positive for "amphetamine" or "methamphetamine" on drug screening tests. While the amphetamine metabolites may contribute to<unk> 's ability to inhibit reuptake of the neurotransmitters dopamine and norepinephrine, they have also been associated with orthostatic hypotension and hallucinations. The amphetamine metabolites are hydroxylated and, in phase II, conjugated by glucuronyltransferase. A newer anti-Parkinson MAO-B inhibitor, rasagiline, metabolizes into 1(R)-aminoindan, which has no amphetamine-like characteristics. Patch Following application of the patch to humans, an average of 25% to 30% of the<unk>  content is delivered systemically over 24 hours. Transdermal dosing results in significantly higher exposure to<unk>  and lower exposure to all metabolites when compared to oral dosing; this is due to the extensive first-pass metabolism of the pill form and low first-pass metabolism of the patch form. The site of application is not a significant factor in how the drug is distributed. In humans,<unk>  does not accumulate in the skin, nor is it metabolized there.
Selegiline
Rasagiline
Perhexiline
Bedaquiline
Deutetrabenazine
Rimonabant
Belinostat
Tetrabenazine