Harman (1-methyl-β-carboline) is a natural inhibitor of monoamine oxidase type A in rats

Harman (1-methyl-β-carboline) displaces [ 3H]pargyline in vitro from high affinity binding sites on membranes from cerebral cortex, provided that experimental conditions are chosen under which [ 3H]pargyline labels selectively monoamine oxidase type A. Norharman (β-carboline) is a much weaker displacing compound. It is well known that the type A enzyme can be blocked irreversibly in vivo by treatment of rats with clorgyline. Under these conditions no specific binding of [ 3H]harman and [ 3H]pargyline to monoamine oxidase type A was detected in brain, whereas the specific binding was reduced to 5% in liver tissue. The in vitro and ex vivo experiments suggest that there is a specific binding site for harman on monoamine oxidase type A, thereby extending earlier in vitro findings. It has been postulated that harman operates as a natural inhibitor of monoamine oxidase type A in mammals. The present study demonstrates that harman and norharman occur in rat brain, blood plasma, heart, kidney and liver. It further shows that pretreatment with clorgyline induces a time-dependent increase in the blood plasma levels of harman, suggesting the displacement of harman from the enzyme in tissue with its subsequent delivery into the blood. These findings strongly support the hypothesis based on in vitro experiments, that harman binds reversibly to the active site of monoamine oxidase type A in vivo. Dietary sources for mammalian harman play probably only a minor role, because the concentrations in beer and wine as well as other foodstuffs are too low to contribute substantially to endogenous levels of harman.