Overview of the CNS pharmacology of BW 1370U87: A chemically novel, reversible, selective MAO-A inhibitor with potential to be a new antidepressant drug

Autor: Greg C. Rigdon, Otto Beek, Robert M. Ferris, G. W. Kraemer, Ronald M. Norton, Helen L. White, Barrett R. Cooper, James L. Howard
Rok vydání: 1992
Předmět:
Zdroj: Drug Development Research. 25:181-190
ISSN: 1098-2299
0272-4391
DOI: 10.1002/ddr.430250302
Popis: BW 1370U87 is a potent, reversible, selective inhibitor of rat and human brain MAO-A with a competitive mechanism of action. The ED50 of BW 1370U87 for inhibition of MAO-A in rat brain is 8 mg/kg after oral administration, and the duration of action exceeds 7 hr. The ED80 dose for inhibition of MAO-A (20 mg/kg) elevates NE, DA, and 5-HT levels in brains of rats without significantly potentiating the blood pressure effects of a 15 mg/kg oral dose of tyramine. This dose of tyramine, extrapolated to man, exceeds the amount that could be consumed at one time from dietary sources. No inhibition of MAO-B has been observed with BW 1370U87 either in vitro or ex vivo. BW 1370U87 was effective in the 5-hydroxytryptophan potentiation test over the dose range that produced MAO-A inhibition in brain in both rats and mice, and it reduced swim stress induced immobility in the Porsolt test. The compound has positive effects on abnormal social behavior produced by early social deprivation in the rhesus monkey. BW 1370U87 had no adverse cardiovascular effects in dogs or rats. It also had no significant pharmacological effects on various isolated tissue preparations and did not cause changes in the neuronal transport or the receptor systems which mediate the antidepressant effects or side effects of the tricyclic antidepressants. An acute oral dose 100 times that which produced an 80% inhibition of brain MAO-A exhibited no signs of toxicity. BW 137OU87 appears to be a safe reversible MAO-A inhibitor with potential for treating depression, anxiety conditions, panic, phobias, obsessive compulsive behaviors, and borderline personality disorders.
Databáze: OpenAIRE
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