L-deprenyl: nitric oxide production and dilation of cerebral blood vessels.
The monoamine oxidase-B inhibitor L-deprenyl (Selegiline) is effective in treating Parkinson's disease and possibly Alzheimer's disease. The neuroprotective property of L-deprenyl may be unrelated to the inhibition of monoamine oxidase-B. Since nitric oxide (NO) modulates activities including cerebral blood flow and memory, we examined the effect of L-deprenyl on NO. L-Deprenyl induced rapid increases in NO production in brain tissue and cerebral vessels. Vasodilation was produced by endothelial NO-dependent as well as NO-independent mechanisms in cerebral vessels. The drug also protected the vascular endothelium from the toxic effects of amyloid-beta peptide. These novel actions of selegiline may protect neurons from ischemic or oxidative damage and suggest new therapeutic applications for L-deprenyl in vascular and neurodegenerative diseases.
Woodlands Medical and Research Center, Oldsmar, FL 45677, USA.
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Thomas
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McLendon
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D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis*; D012642:Selegiline / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014664:Vasodilation / Q000187:drug effects*
D016229:Amyloid beta-Peptides; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D009569:Nitric Oxide