Cipralisant

Cipralisant (GT-2331) is an orally active, low-toxicity, potent, selective, high affinity histamine H3 receptor full antagonist in vivo, and an agonist in vitro, with a pK_i of 9.9 for histamine H3 receptor and a K_i of 0.47 nM for rat histamine H3 receptor. Cipralisant has the potential for attention-deficit hyperactivity disorder research^[1][2][3][4]. Cipralisant is a click chemistry reagent, itcontains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. IC50 & Target: pKi: 9.9 (Histamine H3 receptor)^[4].
Ki: 0.47 nM (Rat histamine H3 receptor)^[3] In Vitro: Cipralisant behaves as a full agonist on adenylyl cyclase inhibition. Cipralisant (HEK cells) potently inhibits forskolin-induced cAMP accumulation, showing that Cipralisant works as a potent full histamine H3 receptor agonist. Cipralisant increases the basal [³⁵S]GTPγS binding activities in membranes from HEK cells expressing the rat histamine H3 receptor (EC₅₀, 5.6 nM)^[3]. In Vivo: Cipralisant (0.3~30 mg/kg; s.c.) enhances acquisition over five trials, reaching significance at 1 mg/kg^[2].
Cipralisant (10 mg/kg; p.o.) completely blocks R-α-methylhistamine-induced drinking^[3].
Cipralisant promotes wakefulness in the rat. Cipralisant potently and significantly improves performance in the repeated acquisition model, in line with its high affinity for the rat H3 receptor and good CNS penetration. Cipralisant does not appear to be as efficacious as 3 mg/kg ciproxifan at its maximally effective dose ^[2]. Cipralisant behaves as a partial agonist in a rat brain synaptosome model^[3].