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The Influence Of Drug-Tissue Interactions On The Inhibition Of Monoamine Oxidase By Pheniprazine And Iproniazid


, : The Influence Of Drug-Tissue Interactions On The Inhibition Of Monoamine Oxidase By Pheniprazine And Iproniazid. Journal of Pharmacology and Experimental Therapeutics 142: 141-146

The anti-monoamine oxidase (MAO) properties of pheniprazine (PIH) and iproniazid in the supernatant fractions of homogenates exposed to the inhibitors were investigated. In the in vitro experiments it was shown that PIH disappeared rapidly from the supernatant fluid of brain homogenate . This effect was apparently nonenzymic, for boiled brain homogenate was even more active in inactivating PIH. Liver tissue was also effective but to a lesser degree. The disappearance of active PIH from the supernatant correlated well with the rapid onset of peak inhibition produced by this compound. Iproniazid disappearance was not evident with low concentrations of tissues, but with larger amounts of liver homogenate, an early loss of MAO inhibitory activity was seen in the supernatant fraction. This was followed by a sudden increase in inhibitor activity and was maintained throughout the experimental period. Concomitant assay of the enzyme indicated a progressively increasing inhibition of the MAO which reached maximum after 2 hours of preincubation with the inhibitor. The supernatant MAO inhibitory activity of brain and liver homogenates prepared from rats pretreated with PIH disappeared rapidly, and within 60 minutes detectable amounts were essentially absent. In iproniazid pretreated animals supernatant MAO inhibitory activity persisted for 12 to 18 hours after drug administration, although peak levels occurred some 1 to 2 hours after injection. The rate of disappearance of PIH and iproniazid activity from the supernatant probably is associated with the time of onset of peak activity of the 2 compounds, under both in vitro and in vivo conditions.

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PMID: 14085495


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