Behaviour of (-)-deprenyl and its analogues

J Neural Transm Suppl. 1994:41:167-75. doi: 10.1007/978-3-7091-9324-2_23.

Abstract

A number of new deprenyl analogues were synthesized during the last decades and structure-activity relationship studies were carried out with the compounds. Among these derivatives U-1424 [N-methyl-N-propargyl-(2-furyl-1-methyl)-ethyl ammonium] and J-508 [N-methyl-N-propargyl-(1-indanyl) ammonium] preserved the selectivity to MAO-B, but the former is slightly less potent inhibitor of the enzyme, while J-508 is more effective than the parent compound. The studies led us to the conclusion that, in the case of a selective and irreversible inhibitor, it is not a proper aim to search for a more potent inhibitor than deprenyl. Nevertheless, the effects of the new derivatives independent of the enzyme inhibitory potency can be beneficial. In this respect p-fluoro-deprenyl (PFD) seems to be promising. In addition to the enzyme inhibitory action, the compounds possess reversible effects e.g. inhibition of uptake and release of the synaptic processes. The fate of the drugs in the body including metabolism is also an important aspect of drug action. PFD is slightly less potent inhibitor of MAO-B in vitro than deprenyl but it maintains a more prolonged concentration in tissues. Its metabolites (p-fluoro-amphetamine and p-fluoro-methamphetamine) are more effective inhibitors of uptake than the parent compound. In respect of the release of transmitter amines, the (+)-isomers of the metabolites are more potent but we did not find significant differences between the uptake inhibitory potencies of the stereoisomers. PFD is more effective to protect the neurodegenerative effects of the noradrenergic neurotoxin DSP-4, compared to deprenyl.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood / metabolism
  • Brain / metabolism
  • Monoamine Oxidase Inhibitors / blood
  • Monoamine Oxidase Inhibitors / pharmacokinetics
  • Monoamine Oxidase Inhibitors / pharmacology
  • Rats
  • Selegiline / analogs & derivatives*
  • Selegiline / chemistry
  • Selegiline / pharmacokinetics
  • Selegiline / pharmacology*
  • Structure-Activity Relationship

Substances

  • Monoamine Oxidase Inhibitors
  • 4-fluorodeprenyl
  • Selegiline