Procognitive activity of nitric oxide inhibitors and donors in animal models.

Abstract

Nitric oxide is a small gaseous molecule that plays important roles in the majority of biological functions. Impairments of NO-related pathways contribute to the majority of neurological disorders, such as Alzheimer's disease (AD), and mental disorders, such as schizophrenia. Cognitive decline is one of the most serious impairments accompanying both AD and schizophrenia. In the present study, the activities of NO donors, slow (spermine NONOate) or fast (DETANONOate) releasers, and selective inhibitor of neuronal nitric oxide synthase N(ω)-propyl-l-arginine (NPLA) were investigated in pharmacological models of schizophrenia and AD. Cognitive impairments were induced by administration of MK-801 or scopolamine and were measured in novel object recognition (NOR) and Y-maze tests. The compounds were investigated at doses of 0.05-0.5 mg/kg. The dose-dependent effectiveness of all the compounds was observed in the NOR test, while only the highest doses of spermine NONOate and NPLA were active in the Y-maze test. DETANONOate was not active in the Y-maze test. The impact of the investigated compounds on motor coordination was tested at doses of 0.5 and 1 mg/kg. Only NPLA at a dose of 1 mg/kg slightly disturbed motor coordination in animals.

• Authors: Paulina Cieślik, Leszek Kalinowski, Joanna M Wierońska
• Journal: Nitric oxide : biology and chemistry (Nitric Oxide) Vol. 119 Pg. 29-40 (02 01 2022) ISSN: 1089-8611 [Electronic] United States
• PMID: 34896554 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Inc. All rights reserved.

Chemical References

• Enzyme Inhibitors
• N(omega)-propylarginine
• Nitric Oxide Donors
• Nitroso Compounds
• Nootropic Agents
• spermine nitric oxide complex
• 2,2'-(hydroxynitrosohydrazono)bis-ethanamine
• Spermine
• Nitric Oxide
• Dizocilpine Maleate
• Arginine
• Scopolamine
• Nitric Oxide Synthase Type I
• Nos1 protein, mouse

Topics

• Alzheimer Disease (chemically induced, drug therapy)
• Animals
• Arginine (analogs & derivatives, therapeutic use)
• Cognitive Dysfunction (chemically induced, drug therapy)
• Dizocilpine Maleate
• Enzyme Inhibitors (therapeutic use)
• Male
• Mice
• Nitric Oxide (antagonists & inhibitors, metabolism)
• Nitric Oxide Donors (therapeutic use)
• Nitric Oxide Synthase Type I (antagonists & inhibitors)
• Nitroso Compounds (therapeutic use)
• Nootropic Agents (therapeutic use)
• Open Field Test (drug effects)
• Rotarod Performance Test
• Schizophrenia (chemically induced, drug therapy)
• Scopolamine
• Spermine (analogs & derivatives, therapeutic use)