I. Stern, R. D. Hollifield, S. Wilk
Jun 1, 1967
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0
Influential Citations
43
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Journal
The Journal of pharmacology and experimental therapeutics
Abstract
Furazolidone (N-(5-nitro-2-furfurylidene)-3-amino-2-oxazolidinone) in saturated solution in vitro did not affect rat liver monoamine oxidase (MAO). After a single oral dose in rats, however, decreased liver mitochondrial MAO was observed in about 4 hr, and maximal inhibition occurred in 16 to 24 hr. Enzyme activity returned to normal over approximately 21 days. A classical dose-response curve was elicited by oral administration of 2 (no effect) to 100 (complete inhibition) mg/kg, with 50% inhibition being given by 20 mg/kg. Inhibition in brain and liver was cumulative. Combining sonically-lysed mitochondria from control or dosed animals had no effect on the MAO activity of either. A study of nitrofurans and other compounds indicated that the unsubstituted 3-amino-2-oxazolidinone moiety was essential for inhibition in vivo but was inactive in vitro. Of several postulated degradation products of 3-amino-2-oxazolidinone, only 2-hydroxyethyl hydrazine (HEH) fulfilled known structural requirements for MAO inhibition. At 10 -6 M in vitro HEH gave 50% inhibition of mitochondrial MAO; 30 min after oral administration of 10 mg/kg, almost complete loss of MAO activity occurred. From the above results, it is proposed that MAO inhibition observed after furazolidone administration may be a result of metabolism in part to HEH.