INTERACTION OF TETRAHYDROSTILBAZOLES WITH MONOAMINE-OXIDASE-A AND MONOAMINE-OXIDASE-B

1-Methyl-1,2,3,6-tetrahydrostilbazole (MTHS) and its analogs are oxidi zed by monoamine oxidase (MAO) A at slow rates comparable to that for the structurally similar neurotoxin, 1-methyl-4 phenyl-1,2,3,6-tetrahy dropyridine, but the rates of oxidation by MAO B vary over a wide rang e depending on the structure of the analog. MAO A oxidation of ah of t he analogs yielded nonhyperbolic kinetic patterns, with little differe nce between the cis and trans isomers. In contrast MAO B showed hyperb olic kinetics and distinct stereoselectivity for the cis isomers. The corresponding pyridinium forms of trans-MTHS and its analogs were more potent inhibitors of MAO A (K-i values between 0.3 and 5 mu M) than o f MAO B, for which the K-i values varied greatly. The data suggest tha t the stringency of the MAO A active site for the geometry of the subs trate molecule is less strict than that of MAO B. With MAO B, any subs titution on the phenyl ring can lead to dramatic changes in the substr ate properties which may be explained by the different orientation of substrate at the active site of the enzyme. Molecular geometry but not the effects of the substituents was shown to be an important factor i n determining the effectiveness of substrate oxidation by MAO B.