Mechanism of MAO Inhibition by Two Trichlorophenoxypropylamines

• Published in: Japanese Journal of Pharmacology Vol. 76; no. suppl.1; p. 140
• Main Authors: ARAI, Yuichiro, UCHIDA, Naoki, YASUHARA, Hajime, SATOH, Nobunori, TADANO, Takeshi, KISARA, Kensuke, KINEMUCHI, Hiroyasu
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1998
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)40671-9

Monoamine oxidase (MAO), amine-metabolizing enzyme, is classified into two forms, MAO-A and -B, by the different sensitivities to inhibition by the inhibitors (clorgyline and 1-deprenyl) and by the different molecular sequencies. Clorgyline is a highly selective, irreversible MAO-A inhibitor. We synthesized its modified chemical compounds of 2,4,5- and 2,4,6-trichlorophenoxypropylamine and determined their inhibitory activities towards MAO in rat brain. Both compounds strongly inhibited MAO-A and -B activities. The inhibitions of MAO-B by 2,4,5,- and of MAO-A and -B by 2,4,6- were decreased after preincubation. The preincubation time-dependent manner suggests that these would be substrates of MAO. In contrast, the inhibition of MAO-A by 2,4,5- was increased after the preincubation. After 90 min preincubation with 2,4,5-, the enzyme preparation was dialysed for about 24 hrs at 4℃, and the recovery of the MAO-A activity was determined. But, the degree of inhibition was not recovered. This indicates the possibility of the 2,4,5- compound being an irreversible MAO-A inhibitor.