Deprenyl: from chemical synthesis to neuroprotection.
During the last decades (-)-deprenyl has become the golden standard of MAO-B inhibitors. It possesses dopamine potentiating and antioxidant properties; however, its effects cannot be explained solely by the enzyme inhibitory action. (-)-Deprenyl prevents the toxicity of certain selective neurotoxins and recently it was demonstrated to increase cell-cell adhesion as well. The complexity of its pharmacological effects reflects the action of both the parent compound and the active metabolites. (-)-Deprenyl and related propargylamines (DRPs) show neuroprotective features in a variety of in vitro and in vivo models that is dependent on the propargyl moiety. The main presumptive targets to date include glyceraldehyde-3-phosphate dehydrogenase, poly(ADP-ribose) polymerase, some kinase cascades, as well as pro- and antiapoptotic proteins, beside the inhibition of MAO-B. The antiapoptotic activity of DRPs converges upon the maintenance of mitochondrial integrity, due to the initiation of a complex transcriptional program, the details of which are yet to be elucidated.
Magyar
K
K
Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary. kalman.magyar@net.sote.hu
Pálfi
M
M
Jenei
V
V
Szöko
E
E
D000818:Animals; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D012642:Selegiline / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*
D018696:Neuroprotective Agents; D012642:Selegiline