Inhibition of the neuronal nitric oxide synthase potentiates homocysteine thiolactone-induced seizures in adult rats.

Abstract

Nitric oxide (NO), one of the gaseous neurotransmitters, is produced in reaction catalyzed by family of NO synthases (NOS). The involvement of neuronal NOS (nNOS) in seizures induced by homocysteine thiolactone has not been studied. Therefore, the aim of this study was to determine the effects of 7-nitroindazole, a selective nNOS inhibitor, on behavioral manifestations of homocysteine - induced seizures in adult rats. Adult male Wistar albino rats were treated with 7-nitroindazole (25, 50 and 75 mg/kg, i.p.) 30 min before injection of subconvulsive dose of homocysteine (D,L homocysteine thiolactone 5.5 mmol/kg, i.p.). Convulsive behavior was assessed during 90 min upon homocysteine administration by the following parameters: seizure incidence, duration of latency, number of seizure episodes per rat and their severity. Severity of seizures was evaluated using a descriptive scale graded from 0 to 4. It was shown that 7-nitroindazole increased seizure incidence, shortened latency time to first seizure, increased number of seizure episodes per rat and increased severity of seizures induced by homocysteine in rats. 7- nitroindazole in dose of 25 mg/kg led to a statistically significant increase in the seizure incidence and number of seizure episodes per rat, while doses of 50 and 75 mg/kg significantly increased severity of homocysteine-induced seizures. It could be concluded that inhibition of nNOS by 7-nitroindazole potentiates seizures induced by homocysteine in rats.

• Authors: Dragan Hrncić, Aleksandra Rasić-Marković, Danijela Krstić, Djuro Macut, Veselinka Susić, Dragan Djuric, Olivera Stanojlović
• Journal: Medicinal chemistry (Shariqah (United Arab Emirates)) (Med Chem) Vol. 8 Issue 1 Pg. 59-64 (Jan 2012) ISSN: 1875-6638 [Electronic] Netherlands
• PMID: 22420552 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Indazoles
• Homocysteine
• homocysteine thiolactone
• Nitric Oxide Synthase Type I
• 7-nitroindazole

Topics

• Animals
• Behavior, Animal (drug effects)
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (pharmacology)
• Homocysteine (administration & dosage, analogs & derivatives, pharmacology)
• Indazoles (administration & dosage, pharmacology)
• Male
• Neurons (drug effects, enzymology, metabolism)
• Nitric Oxide Synthase Type I (antagonists & inhibitors, metabolism)
• Rats
• Rats, Wistar
• Seizures (chemically induced, metabolism)