Ring-substituted analogues of tranylcypromine as monoamine oxidase inhibitors.

ABSTRACT

4-Fluorotranylcypromine and 4-methoxytranylcypromine, in which the 4-position of the phenyl ring is protected from metabolic ring hydroxylation, were tested for their ability to inhibit, relative to tranylcypromine, monoamine oxidase (MAO) -A and -B in rat brain after administration of low doses (1.2 and 3.7 mumol/kg) of the drugs. One hour after intraperitoneal injection of the lower dose, tranylcypromine was weaker than 4-fluorotranylcypromine and 4-methoxytranylcypromine at inhibiting MAO-A. After long-term (28 day) administration of a dose of 3.7 mumol/kg/day (administered via osmotic minipumps), 4-fluorotranylcypromine had a slightly stronger inhibitory effect on MAO-B than did the other two drugs. At the same time and dose both 4-substituted analogues were slightly more potent inhibitors of MAO-A than was tranylcypromine. After 28 days of administration at a daily dose of 1.2 mumol/kg/day, both analogues produced greater inhibition of MAO-A and -B than did tranylcypromine. 4-Methoxytranylcypromine and 4-fluorotranylcypromine were similar in their extent of inhibition of MAO-B but the former was more potent than the latter at inhibition MAO-A.