Inhibition of neuronal nitric oxide synthase protects against MPTP toxicity.
Previous work showed that several relatively specific inhibitors of neuronal nitric oxide synthase (nNOS) produce protection against MPTP induced dopaminergic toxicity. We examined whether a highly specific novel inhibitor of nNOS, ARRI 7338, could also protect against MPTP toxicity. ARR17338 produced dose-dependent significant protection against MPTP induced depletion of dopamine and protected against MPTP induced depletions of tyrosine hydroxylase immunostained neurons in the substantia nigra. These results provide further evidence that inhibitors of nNOS may be useful for the treatment of Parkinson's disease.
Klivenyi
P
P
Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Andreassen
O A
OA
Ferrante
R J
RJ
Lancelot
E
E
Reif
D
D
Beal
M F
MF
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D044005:Tetrahydroisoquinolines; D013876:Thiophenes / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C410223:ARRI 7338; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D018696:Neuroprotective Agents; D044005:Tetrahydroisoquinolines; D013876:Thiophenes; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine