Effects of two substituted hydrazine monoamine oxidase (MAO) inhibitors on neurotransmitter amines, gamma-aminobutyric acid, and alanine in rat brain

J Pharm Sci. 1993 Sep;82(9):934-7. doi: 10.1002/jps.2600820912.

Abstract

Time- and dose-response analyses were undertaken to investigate the effects of the substituted hydrazine monoamine oxidase (MAO) inhibitors iproniazid and nialamide on the following: MAO-A and -B activity; levels of gamma-aminobutyric acid (GABA), alanine (ALA), and the neurotransmitter amines dopamine, noradrenaline, and 5-hydroxytryptamine (serotonin) and their acid metabolites; and the activity of GABA-transaminase and ALA-transaminase. The results showed that these drugs are relatively potent MAO inhibitors but, unlike the unsubstituted hydrazine MAO inhibitor phenelzine, they do not produce increased GABA and ALA levels in brain. These experiments suggest that a free hydrazine group is necessary for MAO inhibitors to also have marked effects on GABA and ALA.

MeSH terms

  • Alanine / metabolism*
  • Animals
  • Biogenic Monoamines / metabolism*
  • Brain Chemistry / drug effects*
  • Dose-Response Relationship, Drug
  • Hydrazines / pharmacology*
  • Iproniazid / pharmacology
  • Male
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Neurotransmitter Agents / metabolism
  • Nialamide / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Biogenic Monoamines
  • Hydrazines
  • Monoamine Oxidase Inhibitors
  • Neurotransmitter Agents
  • gamma-Aminobutyric Acid
  • Iproniazid
  • Alanine
  • Nialamide