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In vivo comparison of the effects of inhibition of MAO-A versus MAO-B on striatal L-DOPA and dopamine metabolism

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Summary

Utilizing the cerebral microdialysis technique, we have compared in vivo the effects of selective MAO-A, MAO-B, and nonselective MAO inhibitors on striatal extracellular levels of dopamine (DA) and DA metabolites (DOPAC and HVA). The measurements were made in rats both under basal conditions and following L-DOPA administration. Extracellular levels of dopamine were enhanced and DA metabolite levels strongly inhibited both under basal conditions and following L-DOPA administration by pretreatment with the nonselective MAO inhibitor pargyline and the MAO-A selective inhibitors clorgyline and Ro 41-1049. The MAO-B inhibitor deprenyl had no effect on basal DA, HVA, or DOPAC levels. Nervertheless, deprenyl significantly increased DA and decreased DOPAC levels following exogenous L-DOPA administration, a finding compatible with a significant glial metabolism of DA formed from exogenous L-DOPA. We conclude that DA metabolism underbasal conditions is primarily mediated by MAO-A. In contrast, both MAO-A and MAO-B mediate DA formation when L-DOPA is administered exogenously. The efficacy of newer, reversible agents which lack the “cheese effect” such as Ro 41-1049 are comparable to the irreversible MAO-A inhibitor clorgyline. The possible relevance of these findings for the treatment of Parkinson's disease is discussed.

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Brannan, T., Prikhojan, A., Martínez-Tica, J. et al. In vivo comparison of the effects of inhibition of MAO-A versus MAO-B on striatal L-DOPA and dopamine metabolism. J Neural Transm Gen Sect 10, 79–89 (1995). https://doi.org/10.1007/BF02251224

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Keywords

  • Dopamine
  • L-DOPA
  • monoamine oxidase
  • deprenyl
  • pargyline
  • clorgyline
  • Ro 41-1049
  • MAO-A
  • MAO-B Parkinson's disease
  • cerebral microdialysis