Epilepsy is a multifaceted
neurological disorder which severely affects neuronal function. Some patients may experience
status epilepticus (SE), a life-threatening state of ongoing seizure activity linked to
cognitive dysfunction, necessitating an immediate intervention. The potential of
histamine H3 receptors in several neuropsychiatric diseases including
epilepsy is well recognized. In the current study, we aimed to explore the effect of H3R antagonist E177 on prevention and termination of
pilocarpine (PLC)-induced SE in rats as well as evaluating the effects of E177 on the levels of oxidative stress in hippocampus tissues. The results showed that the survival rate of animals pretreated with E177 (5 and 10 mg/kg, intraperitoneal (i.p.)) was significantly increased during the first hour of observation, and animals were protected from SE incidence and showed a prolonged average of latency to the first seizure when compared with animals pretreated with PLC (400 mg/kg, i.p.). Moreover, the protective effect of E177 (10 mg/kg) on SE was partially reversed when rats were co- administered with H3R agonist R-(α)-methylhistamine (RAM) and with the H2R antagonist
zolantidine (ZOL), but not with the H1R antagonist
pyrilamine (PYR). Furthermore, pretreatment with E177 (5 and 10 mg/kg) significantly decreased the abnormal levels of
malondialdehyde (MDA), and increased levels of
glutathione (GSH) in the hippocampal tissues of the treated rats. However, E177 failed to modulate the levels of
catalase (CAT),
superoxide dismutase (SOD), or
acetylcholine esterase activity (AChE). Our findings suggest that the newly developed H3R antagonist E177 provides neuroprotection in a preclinical PLC-induced SE in rats, highlighting the histaminergic system as a potential therapeutic target for the therapeutic management of SE.