Effects of clobenpropit on pentylenetetrazole-kindled seizures in rats

Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases

“…As illustrated in Table 3, numerous H3R antagonists were found to attenuate or delay convulsions in several electrical, chemical or genetic preclinical models of epilepsy. These experimental anticonvulsive observations of H3R antagonists seem to largely depend on H1R activation and increased histamine release since the protective effects observed were reversed by co-administration of several CNS-penetrant H1R antagonists [141,155,156]. Furthermore, bicuculline, a GABAA receptor antagonist, significantly diminished clobenpropit-induced inhibition of amygdaloid kindling [157].…”

International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors

“…Thioperamide is highly potent at rat H 3 receptors with K i = 4.3 nM (Arrang et al, 1987a;Hill et al, 1997) that has been found broadly effective in vivo in a large number of behavioral models, including elevated plus maze learning, Morris water maze, Barnes maze (Miyazaki et al, 1995;Komater et al, 2005), and others. Clobenpropit (41) is likewise highly potent in vitro, with pA 2 = 9.92 in the guinea pig ileum assay (Eriks et al, 1992) and activity in vivo, e.g., in models of working memory, seizure, and Alzheimer's disease (Yokoyama et al, 1994;Zhang et al, 2003;Harada et al, 2004;Huang et al, 2004;Bardgett et al, 2011). Clobenpropit and thioperamide, however, also have potent activity at H 4 receptors (Lim et al, 2009), and thioperamide also is active at 5HT 3 receptors (Leurs et al, 1995b).…”

Histaminergic Neurons Protect the Developing Hippocampus from Kainic Acid-Induced Neuronal Damage in an Organotypic Coculture System

“…In accordance, the first-generation H 1 receptor antagonists have elicited epileptiform activity (Gerald and Richter, 1976;Yokoyama et al, 1996;Kamei et al, 2000;Fujii et al, 2003), controlling its occurrence in particular in the immature brain (Yokoyama, 2001). H 3 receptor antagonists, which block the H 3 autoreceptor function, are suggested to decrease seizure activity by increasing histamine release (Yokoyama et al, 1993(Yokoyama et al, , 1994Kamei, 2001;Zhang et al, 2003).…”