Mechanisms of action Like the older antiparkinson drugs selegiline and rasagiline,<unk>  is a selective monoamine oxidase B inhibitor, reducing degradation of dopamine; in contrast to the other two, its action is reversible.<unk>  also inhibits glutamate release and dopamine and serotonin reuptake. It binds to the sigma receptors as well, with IC50 values for binding inhibition of 19 nM for σ1 and 1,590 nM for σ2. Additionally, it blocks sodium and calcium channels, the relevance of which for its antiparkinson action is however unknown. Pharmacokinetics<unk>  is absorbed quickly and nearly completely from the gut and reaches highest blood plasma concentrations after 1.8 to 2.8 hours. There is no relevant first-pass metabolism; total bioavailability is 95%. The substance is bound to plasma proteins to 88–90%. The metabolism is not well understood. The principal step is mediated by amidases which have not been identified, and produces<unk>  acid (NW-1153). Other relevant metabolites are O-debenzylated<unk>  (NW-1199), the N-dealkylated amine which is then oxidized to a carboxylic acid (NW-1689), and the glucuronide of the latter. In tests with liver microsomes, dealkylation seemed to be mediated by CYP3A4, but other CYP enzymes appear to be involved as well.<unk>  acid binds to the organic anion transporter 3 (OAT3), but this has probably no clinical relevance.<unk>  itself transiently binds to ABCG2. No other transporter affinities have been found in preliminary studies.<unk>  is eliminated, mainly (>90%) in form of its metabolites, via the kidney, with an elimination half-life of 20 to 30 hours. Only 1.5% are found in the stool. Metabolism pathways of<unk> . Enzymes: CYP = cytochrome P450, MAO-A = monoamine oxidase A, ALDH = aldehyde dehydrogenases, UGT = UDP-glucuronosyltransferases. Gluc = acyl glucuronide.
Safinamide
Pyrazinamide
Ethambutol
Isoniazid
Oxepanoprolinamide
Rifampicin
Plazomicin
Rifabutin