Modulatory effect of opioid ligands on status epilepticus and the role of nitric oxide pathway.

Abstract

Epilepsy is a chronic disorder that causes unprovoked, recurrent seizures. Status epilepticus (SE) is a medical emergency associated with significant morbidity and mortality. Morphine has been the cornerstone of pain controlling medicines for a long time. In addition to the analgesic and opioid responses, morphine has also revealed anticonvulsant effects in different epilepsy models including pentylenetetrazole (PTZ)-induced seizures threshold. Some authors suggest that nitric oxide (NO) pathway interactions of morphine explain the reason for its pro or anticonvulsant activities. To induce SE, injection of a single dose of lithium chloride (127 mg/kg, intraperitoneal (i.p.)) 20 h before pilocarpine (60 mg/kg, i.p.) was used. Administration of morphine (15 mg/kg, i.p.) inhibited the SE and decreased the mortality in rats when injected 30 min before pilocarpine. On the other hand, injection of L-NG-nitro arginine methyl ester (L-NAME, a nonselective NO synthase (NOS) blocker; 10 mg/kg, i.p.), 7-nitroindazole (7-NI, a neuronal NOS (nNOS) blocker; 30 mg/kg, i.p.), and aminoguanidine (AG, an inducible NOS (iNOS) blocker; 50 mg/kg, i.p.) 15 min before morphine, significantly reversed inhibitory effect of morphine on SE. Subsequently, measurement of nitrite metabolite levels in the hippocampus of SE-induced rats displayed high levels of nitrite metabolite for the control group. However, after injection of morphine in SE-induced rats, nitrite metabolite levels reduced. In conclusion, these findings demonstrated that NO pathway (both nNOS and iNOS) interactions are involved in the anticonvulsant effects of morphine on the SE signs and mortality rate induced by lithium-pilocarpine in rats.

• Authors: Shahab Meskinimood, Nastaran Rahimi, Hedyeh Faghir-Ghanesefat, Mahdi Gholami, Mohammad Sharifzadeh, Ahmad Reza Dehpour
• Journal: Epilepsy & behavior : E&B (Epilepsy Behav) Vol. 101 Issue Pt A Pg. 106563 (12 2019) ISSN: 1525-5069 [Electronic] United States
• PMID: 31675604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Analgesics, Opioid
• Anticonvulsants
• Indazoles
• Ligands
• Pilocarpine
• Nitric Oxide
• Morphine
• Nitric Oxide Synthase
• Lithium Chloride
• 7-nitroindazole
• NG-Nitroarginine Methyl Ester
• Pentylenetetrazole

Topics

• Analgesics, Opioid (therapeutic use)
• Animals
• Anticonvulsants (therapeutic use)
• Dose-Response Relationship, Drug
• Indazoles (pharmacology)
• Ligands
• Lithium Chloride (toxicity)
• Male
• Morphine (therapeutic use)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (antagonists & inhibitors, metabolism)
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Pentylenetetrazole (toxicity)
• Pilocarpine (adverse effects)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects, physiology)
• Status Epilepticus (chemically induced, drug therapy, metabolism)