Protective effects of M8‑B, a TRPM8 antagonist, on febrile‑ and pentylenetetrazol‑induced seizures

Abstract

Epilepsy is a life‑threatening disorder that is marked by recurrent seizures. Febrile seizure is a common neurological disorder observed in neonates. In many cases, reducing body temperature can prevent febrile seizure. Transient receptor potential cation channel subfamily M member 8 (TRPM8) is a cation channel that is involved in body thermoregulation. It was reported that M8‑B, a TRPM8 antagonist, can reduce body temperature. Thus, we aimed to investigate the effect of M8‑B on different experimental seizure models. Eight‑day‑old male Wistar rat pups were used for induction of febrile seizure. M8‑B and diazepam were injected intraperitoneally. The rat pups were then transferred to a heated plexiglas chamber and the latency to the first febrile seizure was measured. In addition, different groups of mice were pretreated with M8‑B and received a convulsant dose of pentylenetetrazol (PTZ). Latencies to stages 2 and 4 and duration of stage 5 seizure episodes were measured. Furthermore, the effect of M8‑B on electroshock‑induced seizures was also investigated and hindlimb extension time was measured. The results showed that M8‑B decreased the body temperature of rat pups and increased the latency to the first febrile seizure, implying a significant protective effect. It also induced a significant anticonvulsant effect in PTZ ‑ but not electroshock‑induced convulsions. M8‑B showed anticonvulsant effects in both febrile‑ and PTZ‑induced seizures. M8‑B had a hypothermic effect with significant protective effects on febrile‑ and PTZ‑induced seizures; however, it did not produce similarly protective effects on seizures induced by electroshock.