Neuropharmacological Profile of Gamma-Decanolactone on Chemically-induced Seizure in Mice

Title:Neuropharmacological Profile of Gamma-Decanolactone on Chemically-induced Seizure in Mice

Volume: 18 Issue: 3

Author(s): Pricila Pfluger, Vanessa Rodrigues Coelho, Gabriela Gregory Regner, Lucas Lima da Silva, Karina Martinez, Alan Fonseca, Cassiana Macagnan Viau and Patricia Pereira*

Affiliation:

• Laboratory of Neuropharmacology and Preclinical Toxicology, Postgraduate Program in Biological Sciences: Pharmacology and Therapeutics, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Sarmento Leite 500/305, Porto Alegre, RS, CEP 90050-170,Brazil

Keywords: 4-aminopyridine, gamma-decanolactone, isoniazid, picrotoxin, seizure, monoterpene.

Abstract: Background: Gamma-Decanolactone (GD) is a monoterpene compound that presents anticonvulsant effect in acute and chronic models of epilepsy and it acts as a noncompetitive glutamate antagonist.

Objective: This study evaluated the anticonvulsant profile and the possible mechanism of action of GD in seizures induced by isoniazid (INH; 250 mg/kg), picrotoxin (PCT; 5 mg/kg) and 4- aminopyridine (4-AP; 13 mg/kg) in male mice.

Method: Thirty minutes before the convulsants administration, animals received a single administration of saline, GD (100 or 300 mg/kg) or the positive control diazepam (DZP; 2 mg/kg). The parameters evaluated were the latency to the first seizure and the occurrence of clonic forelimb seizures. The rotarod performance test was used to evaluate the neurotoxicity of GD (300 mg/kg). Also, the DZPinduced sleep test was used.

Results: DZP increased the latency to the first seizure on all used models and decreased the percentage of seizures in two of the three behavioral models. GD was able to prolong the latency to the first seizure and decreased the percentage of seizures induced by INH and 4-AP, but not by PCT. It reduced the latency to fall off the rotarod test only at the time of 30 min. In the DZP-induced sleep test, GD shortened the onset and prolonged the time of sleep.

Conclusion: Our findings suggested that GD reduced the convulsive behavior in the seizure models used here and it could modulate GABA pathways and affect potassium channels directly or indirectly, involving more than one cellular target in the central nervous system.

Cite this article as:

Pfluger Pricila , Coelho Rodrigues Vanessa , Regner Gregory Gabriela , da Silva Lima Lucas , Martinez Karina, Fonseca Alan , Viau Macagnan Cassiana and Pereira Patricia *, Neuropharmacological Profile of Gamma-Decanolactone on Chemically-induced Seizure in Mice, Central Nervous System Agents in Medicinal Chemistry 2018; 18 (3) . https://dx.doi.org/10.2174/1871524918666180611103802