title: Protective effect of 7-nitroindazole against DSP-4 induced noradrenaline depletion in mouse hippocampus.
abstract: 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.
authors.affiliation: Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Szökõ
authors.forename: D
authors.initials: D
authors.lastname: Haberle
authors.forename: A S
authors.initials: AS
authors.lastname: Halász
authors.forename: K
authors.initials: K
authors.lastname: Tekes
authors.forename: K
authors.initials: K
authors.lastname: Magyar
mesh_terms: 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
chemical_list: 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