7-Nitroindazole, a nitric oxide synthase inhibitor, has anxiolytic-like properties in exploratory models of anxiety

doi:10.1007/s002130050309

Paper

7-Nitroindazole, a nitric oxide synthase inhibitor, has anxiolytic-like properties in exploratory models of anxiety

Published Jun 1, 1997 · V. Volke, A. Soosaar, S. Kõks

Psychopharmacology

Q1 SJR score

142

Citations

5

Influential Citations

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Abstract

Abstract The action of the novel nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI) was studied in different exploratory models of anxiety. In the rat plus-maze test, 7-NI potently increased time spent on open arms and percentage of open arm visits in a dose-dependent manner with the minimal effective dose of 40 mg/kg. 7-NI caused an anxiolytic-like effect in the rat social interaction test. The minimal dose increasing social interaction time was 20 mg/kg. However, the drug also produced a clear sedative effect occurring even at smaller doses (10 mg/kg) in the open field test. 7-NI also showed an anxiolytic-like profile in the mouse light-dark compartment test and in the elevated plus-maze test, but the doses required were higher (80–120 mg/kg) than in rat models. Also, the sedative effect occurred at these doses in open field. We failed to demonstrate any effect of L-arginine either in the rat elevated plus-maze test or in the open field test at doses up to 600 mg/kg IP. These results indicate that there are no major interspecies differences between rats and mice in respect of action of 7-NI. The clear anxiolytic-like action of the nitric oxide synthase inhibitor in four different models shows that nitric oxide is involved in the process of anxiety and that NOS could be a new target in developing anxiolytic drugs.

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Animal Study

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Study Snapshot

7-nitroindazole shows anxiolytic-like properties in anxiety models, suggesting nitric oxide plays a role in anxiety and could be a new target for developing anxiolytic drugs.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

7-Nitroindazole, a nitric oxide synthase inhibitor, has anxiolytic-like properties in exploratory models of anxiety

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References

Differential action of 7-nitro indazole on rat brain nitric oxide synthase

7-nitro indazole has differential effects on brain nitric oxide synthase inhibition, with cerebellum and nigral showing the highest inhibition, and recovery from inhibition varies between brain regions.

Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity.

Neuronally derived nitric oxide plays a significant role in MPTP-induced neurotoxicity, suggesting it may play a significant role in the etiology of Parkinson's disease.

Ex Vivo Measurement of Brain Tissue Nitrite and Nitrate Accurately Reflects Nitric Oxide Synthase Activity In Vivo

Ex vivo measurement of brain tissue nitrite and nitrate levels accurately reflects nitric oxide synthase activity in vivo, allowing for rapid assessment of regional distribution and inhibitory effects.

Attenuation of malonate-induced degeneration of the nigrostriatal pathway by inhibitors of nitric oxide synthase

Malonate-induced neurotoxicity in the nigrostriatal pathway is partially mediated by NMDA receptor activation and nitric oxide formation.

The Role of Neuronal Nitric Oxide Synthase in Regulation of Cerebral Blood Flow in Normocapnia and Hypercapnia in Rats

Neuronal nitric oxide synthase plays a crucial role in regulating cerebral blood flow during normocapnia and hypercapnia, with its inhibitor 7-NI reducing resting CBF and hypercapnia-induced CBF response.

Citations

Inhibition of Nitric Oxide Synthesis Prevents the Effects of Intermittent Social Defeat on Cocaine-Induced Conditioned Place Preference in Male Mice

Inhibiting nitric oxide synthesis prevents the long-term potentiation of cocaine-induced conditioned place preference in stressed mice, supporting a specific role of nNOS in social stress effects on drug reward.

Nitric Oxide (NO) Synthase Inhibitors: Potential Candidates for the Treatment of Anxiety Disorders?

Nitric oxide synthase inhibitors (NOSIs) show potential in reducing anxiety, but their anti-anxiety action remains to be established.

Effects of extended-release 7-nitroindazole gel formulation treatment on the behavior of Shank3 mouse model of autism.

The single-dose PSARA gel formulation effectively improves memory, social interaction, and reduces anxiety-like behavior in Shank3 mutant mice, potentially offering a rational design for an effective ASD treatment.

MLN-4760 Induces Oxidative Stress without Blood Pressure and Behavioural Alterations in SHRs: Roles of Nfe2l2 Gene, Nitric Oxide and Hydrogen Sulfide

MLN-4760 causes oxidative damage in the brainstem without affecting blood pressure or behavioral parameters, but activates NO- and H2S-mediated compensatory mechanisms and increases antioxidant, NO-, and H2S-producing enzymes.

Neuronal nitric oxide synthase inhibition accelerated the removal of fluoxetine’s anxiogenic activity in an animal model of PTSD

Adding nNOS inhibitor to subchronic fluoxetine therapy accelerates the removal of fluoxetine's anxiogenic properties, potentially improving anxiety-related behavior in PTSD patients.