Protective effect of 7-nitroindazole against DSP-4 induced noradrenaline depletion in mouse hippocampus.
N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is a selective noradrenaline (NA) uptake blocker, capable of inducing a long-lasting depletion of NA in some noradrenergic axon terminals originating from the locus coeruleus in rodents. Pretreatment with 7-nitroindazole, a fairly selective inhibitor of neuronal nitric oxide synthase in vivo, partially prevented DSP-4 induced NA depletion in mouse hippocampus measured seven days after the neurotoxic insult. Administration of L-arginine, the substrate of nitric oxide synthase, altered neither the NA depletion induced by DSP-4, nor the protective effect of 7-nitroindazole. Inhibition of nitric oxide synthesis by N(G)-nitro-L-arginine methyl ester did not attenuate the NA depleting effect of DSP-4. Thus, the contribution of neuronal nitric oxide synthase inhibition to the protective effect of 7-nitroindazole needs further studies. As 7-nitroindazole did not block NA uptake, this cannot play a part in the protective effect. The possible contribution of monoamine oxidase B enzyme inhibition by 7-nitroindazole to the protective effect is also discussed.
Szökõ
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E
Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
Haberle
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D
Halász
A S
AS
Tekes
K
K
Magyar
K
K
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D009638:Norepinephrine / Q000378:metabolism*; D013566:Sympathomimetics / Q000494:pharmacology
D001596:Benzylamines; D004791:Enzyme Inhibitors; D007191:Indazoles; D018696:Neuroprotective Agents; D013566:Sympathomimetics; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C012102:DSP 4; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine