Ring-substituted analogues of tranylcypromine as monoamine oxidase inhibitors.
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.
Sherry
R L
RL
Neurochemical Research Unit, University of Alberta, Edmonton, Canada.
Baker
G B
GB
Coutts
R T
RT
Mousseau
D D
DD
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014191:Tranylcypromine / Q000031:analogs & derivatives* / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D018377:Neurotransmitter Agents; C055203:4-fluorotranylcypromine; C068589:4-methoxytranylcypromine; D014191:Tranylcypromine; D008995:Monoamine Oxidase