Platelet monoamine oxidase B: use and misuse.
The human platelet in addition to having serotonin (5-HT) receptors, uptake carriers (receptor) and transmitter storage vesicles, primarily possesses mitochondrial monoamine oxidase (MAO) type B. Similar to the major form of MAO in the human brain, this enzyme actively oxidizes A-B and B substrates (tyramine, dopamine, phenylethylamine) as well as the novel secondary amine anticonvulsant, milacemide and dopaminergic neurotoxin, MPTP. 5-HT oxidation is hardly affected by the platelet enzyme and MAO inhibitors have no net effect on its accumulation. MAO-B is selectively inhibited by 1-deprenyl and thus the platelet enzyme may be useful to monitor the anti-Parkinson activity of such drugs, as related to their ability to inhibit brain MAO-B. The oxidation of the anticonvulsant, milacemide, to glycine in vitro and in vivo by MAO-B, may herald new prospects for the development of inert prodrugs capable of being metabolized to neuroactive substances by MAO-B. The plasma levels of their metabolites may be an index of MAO-B activity found in the platelet and brain.
Youdim
M B
MB
Rappaport Family Research Institute, Technion, Haifa, Israel.
D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001792:Blood Platelets / Q000201:enzymology*; D001921:Brain / Q000201:enzymology; D006801:Humans; D001523:Mental Disorders / Q000201:enzymology; D008995:Monoamine Oxidase / Q000097:blood* / Q000502:physiology; D009474:Neurons / Q000201:enzymology / Q000502:physiology; D012701:Serotonin / Q000502:physiology*
D000927:Anticonvulsants; D012701:Serotonin; D008995:Monoamine Oxidase