Parawixin2, a novel non-selective GABA uptake inhibitor from Parawixia bistriata spider venom, inhibits pentylenetetrazole-induced chemical kindling in rats

Abstract

The aims of the present work were to investigate the effects of the repeated administration of Parawixin2 (2-amino-5-ureidopentanamide; formerly FrPbAII), a novel GABA and glycine uptake inhibitor, in rats submitted to PTZ-induced kindling. Wistar rats were randomly divided in groups (n=6-8) for different treatments. Systemic injections of PTZ were administered every 48 h in the dose of 33 mg/kg; i.p., that is sufficient to induce fully kindled seizures in saline i.c.v. treated rats in a short period of time (28 days). Treatments in two types of positive controls (diazepam - DZP and nipecotic acid - NA groups) consisted in daily systemic injections of DZP (2mg/kg; i.p.) or i.c.v. injections of NA (12 μg/μL), while in experimental groups in daily i.c.v. injections of different doses of Parawixin2 (0.15; 0.075; 0.015 μg/μL). Seizures were analyzed using the Lamberty & Klitgaard score and kindling was considered as established after at least three consecutive seizures of score 4 or 5. Cumulative seizure scores for each group were analyzed using repeated measures of ANOVA followed by Tukey test. PTZ induced 4 and 5-score seizures after 12 injections in saline treated rats, whereas daily injection of Parawixin2 inhibited the onset of seizures in a dose dependent manner. Also, the challenging administration of PTZ did not raise seizure score in animals treated with the highest dose of Parawixin2 or those treated with DZP or NA. These findings together with previous data from our laboratory show that Parawixin2 could be a useful probe to design new antiepileptic drugs.

Association of Microtubule Dynamics with Chronic Epilepsy

“…In this case, the first myoclonic jerks (score 2 seizures) were observed after the 2 day administration, and kindling criteria were reached after 12 injections. This is consistent with the finding of Gelfuso et al [11]. Our study revealed that intrahippocampal injection of microtubule-depolymerizing agent exhibited a significant increase in severity of seizures.…”

“…PTZ kindling model was induced according to the method of Gelfuso et al [11]. Chemoconvulsant PTZ (a GABA receptor antagonist, 33 mg/kg, i.p., Sigma-Aldrich, St. Louis, MO, USA) was injected every other day, in the morning period.…”

Pro- and Anticonvulsant Effects of the Ant Dinoponera quadriceps (Kempf) Venom in Mice

“…In addition, Parawixin 2 is a potent anticonvulsant against chemically induced acute seizures (Liberato et al 2006, Gelfuso et al 2007, and showed similar effects against pentylenetetrazol (PTZ)-induced kindling (Gelfuso et al 2013). Further, besides the effects of their isolated toxins, the denatured crude venoms, i.e., venom free of high molecular weight proteins, have also showed anticonvulsant actions.…”

Atlastin‐1 modulates seizure activity and neuronal excitability

“…Mice were kindled by pentylenetetrazol (PTZ) to develop a chronic epileptic mouse model according to previously described methods . Adult C57/BL6 male mice were administered an intraperitoneal injection of a subconvulsive dose of PTZ (35 mg/kg dissolved in 0.9% NaCl pH 7.0) every other day for 30 days and then observed for one hour after each injection.…”