Antiepileptic profile of Parawixin-11, purified from Parawixia bistriata spider venom (Araneae, Araneidae), in Wistar rats

The pharmacological treatment of epilepsy is often complex due to the lack of efficacy in many patients and profound side effects from current drugs, including sedation, motor impairment, and teratogenesis. In the quest for new antiepileptic drugs, animal venoms offer a valuable source of neuroactive molecules targeting ion channels and neurotransmitter receptors. This study investigates the antiepileptic potential of compounds isolated from the venom of the Parawixia bistriata spider. One compound, designated Parawixin-11, demonstrated significant anticonvulsant effects when injected into the cerebral ventricle in a dose-response manner. It effectively countered seizures induced by bicuculline (ED50 0.16 µg/animal), pentylenetetrazole (ED50 0.08 µg/animal), strychnine (ED50 0.05 µg/animal), pilocarpine (ED50 0.10 µg/animal), and NMDA (ED50 0.008 µg/animal). We also assessed whether intracerebroventricular administration of Parawixin-11 caused motor or cognitive impairments in rats using the open field, rotarod, and Morris water maze tests. No differences in exploration or movement were observed with doses of 0.3, 0.2, or 0.1 µg of Parawixin-11. Although there was an increased latency to find the platform during the acquisition phase of the Morris water maze test, no differences in spatial memory retention were noted. Given Parawixin-11’s potency against NMDA-induced seizures, we hypothesize that it may modulate the glutamatergic system, aligning with the mechanisms of several spider-derived polyamines.