Mofegiline is an inhibitor of monoamine oxidase B (MAO-B; IC50 = 3.6 nM for the rat brain mitochondrial enzyme).1 It is selective for MAO-B over MAO-A (IC50 = 680 nM). Mofegiline also inhibits vascular adhesion protein-1 (VAP-1), also known as semicarbazide-sensitive amine oxidase (SSAO), an enzyme that has roles in leukocyte adhesion and transmigration, with an IC50 value of 20 nM for the human enzyme.2 It reduces MPTP-induced decreases in striatal levels of dopamine, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in mice when administered at a dose of 1.25 mg/kg.1 Mofegiline (5 mg/kg) also inhibits LPS-induced increases in bronchoalveolar lavage fluid (BALF) levels of TNF-α in transgenic mice overexpressing VAP-1.
1.Zreika, M., Fozard, J.R., Dudley, M.W., et al.MDL 72,974: A potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's diseaseJ. Neural Transm. Park. Dis. Dement. Sect.1(4)243-254(1989) 2.Foot, J.S., Deodhar, M., Turner, C.I., et al.The discovery and development of selective 3-fluoro-4-aryloxyallylamine inhibitors of the amine oxidase activity of semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1)Bioorg. Med. Chem. Lett.22(12)3935-3940(2012)