Acidic vesicles of the endo-exocytic pathways as targets for some anti-monoamine oxidase drugs

Abstract

Acidic vesicles are cytoplasmatic organelles delimited by a single lipoprotein membrane. They contain a large number of enzymes, mostly acidic hydrolases, catalysing various reactions at optimal acidic pH, capable of participating in intracellular digestion. In this paper, some anti-monoamine oxidase drugs (clorgyline, pargyline, amantadine and deprenyl), utilized as pharmacological treatment in some neurological disorders (e.g., Alzheimer's, Parkinson's etc. diseases), were tested for their ability to influence the pH of the acidic intracellular organelles with the aim of exploring their possible pharmacological action. Of the above mentioned drugs, clorgyline showed the most effective action in modifying the acidic vesicles' internal pH, followed by deprenyl, pargyline and amantadine. The effect was not ascribed to an increased proton conductance, but was most likely due to a weak base-like mechanism, in that they exhibit equilibria among species associated with H(+) ions and species lacking this association.