INHIBITION OF A TYPE-B MONOAMINE-OXIDASE INHIBITOR, (E)-2-(4-FLUOROPHENETHYL)-3-FLUOROALLYLAMINE (MDL-72974A), ON SEMICARBAZIDE-SENSITIVE AMINE OXIDASES ISOLATED FROM VASCULAR TISSUES AND SERA OF DIFFERENT SPECIES

(E)-2-(4-Fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A) has been discovered recently to be a very potent and highly selective type B monoamine oxidase inhibitor. We have found that this inhibitor is also capable of inhibiting semicarbazide-sensitive amine oxidases (SSAOs) obtained from vascular tissues and sera of different species. The inhibition of SSAO by MDL-72974A was irreversible and time dependent. It was competitive without preincubation of the enzyme with the inhibitor. The Ic(50) values were estimated to be 2 x 10(-9) M, 8 x 10(-8) M and 2 x 10(-8) M for SSAO from dog aorta, rat aorta and human umbilical artery, respectively. SSAO obtained from bovine serum was relatively insensitive to MDL-72974A (IC(50) = 3 x 10(-7) M. Following intraperitoneal administration of MDL-72974A, rat brain MAO-B was inhibited with the ED(50) value being about 0.2 mg/kg. Rat aorta SSAO was also inhibited and to a similar extent by the same dose. MDL-72974A is the most potent SSAO inhibitor that has been described thus far.