The dual-active histamine H3 receptor antagonist and acetylcholine esterase inhibitor E100 ameliorates stereotyped repetitive behavior and neuroinflammmation in sodium valproate induced autism in mice

Antagonism of Histamine H3 receptors Alleviates Pentylenetetrazole-Induced Kindling and Associated Memory Deficits by Mitigating Oxidative Stress, Central Neurotransmitters, and c-Fos Protein Expression in Rats

“…Therefore, evaluating numerous oxidative stress markers (e.g., malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD)) of PTZ-kindled animals were carried out to assess the effects of the novel H3R antagonist E177. Furthermore, and amongst all the brain regions, the hippocampus has gained attention in the PTZ model as it contains several distinct neuronal circuits related to seizure genesis [54][55][56][57][58][59]. In the present study, the capability of H3R antagonist E177 to attenuate oxidative stress markers was evaluated in hippocampus tissues of PTZ-kindled rats ( Figure 4A P < 0.05], respectively, and increased GSH levels, with [F (1,10) = 96.74; P < 0.001] and [F (1,10) = 356.1; P < 0.001], respectively, and as compared with PTZ-kindled rats.…”

“…Moreover, chronic pretreatment of RAM to control rats also did not significantly alter oxidative stress statues, with [F ( Several preclinical studies revealed the potential memory-enhancing effect of numerous H3R antagonists [16,18,21,26,[55][56][57][58][59] capable of modulating the release of brain histamine (HA) by antagonizing H3 auto-receptors, and numerous other brain neurotransmitters, e.g., acetylcholine (ACh), γ-aminobutyric acid (GABA), and glutamate (GLU) by antagonizing H3 hetero-receptors in different brain regions [60][61][62].…”

“…Memory retention was examined 24 h later, applying the same protocol of the first day. Prolonged retention TLT was considered as an indicator of impaired memory [21,29,57].…”

Simultaneous Blockade of Histamine H3 Receptors and Inhibition of Acetylcholine Esterase Alleviate Autistic-Like Behaviors in BTBR T+ tf/J Mouse Model of Autism

“…Studies focused on modeling ASD in rodents based on ASD-related behaviors clinically observed in individuals with ASD, such as stereotyped and repetitive behaviors and impairments in social interaction and communication. In this regard, the inbred BTBR T+ tf/J (BTBR) mice has been used as an animal model that garnered attention related to ASD because the BTBR mice exhibits behaviors consistent with the diagnostic categories for ASD, namely social impairment and obsessive/compulsive behaviors, e.g., increased self-grooming, marble burying and disturbed anxiety levels [ 6 , 7 , 8 ].…”

“…Consequently, the imidazole-based H 3 R ligand ciproxifan [ 23 ] and the non-imidazole-based H 3 R antagonist DL77 were described to demonstrate promising enhancing effects on valproic acid-induced ASD-like features in mice [ 24 ]. Moreover, we recently showed that the dual-active H 3 R antagonist and acetylcholine esterase (AChE) inhibitor E100 mitigated oxidative stress and proinflammatory cytokines and alleviated social deficits and stereotyped repetitive behaviors in C57BL/6 mice exposed to valproic acid [ 8 , 25 ]. Furthermore, it has been proposed that histamine H 3 R antagonists/inverse agonists are of potential therapeutic future application for the treatment of CNS-related disorders, such as, Alzheimer’s disease (AD), depression, schizophrenia (SCH) and narcolepsy [ 26 , 27 , 28 ].…”