(R)-(-)-α-Methylhistamine dihydrobromide is a potent, selective, and brain-penetrant agonist of the H3 histamine receptor with high receptor affinity, capable of enhancing memory retention and attenuating cognitive impairment in rat models, making it a valuable pharmacological probe for elucidating central histaminergic signaling and H3 receptor-mediated modulation of learning and memory processes.

H3 receptor:50.3 nM (kd)

(R)-(-)-α-Methylhistamine dihydrobromide is an H3-agonist with over 10 times the potency of histamine (HA). It exhibits weak affinities for H1 and H2 receptors, with pKi values of 4.8 and <3.5, respectively. The compound shows more than 1,000 times selectivity for H3-receptors compared to HA and over 200-fold selectivity over H4 receptors[1].

In mouse and rat models, intraperitoneal (i.p.) administration of (R)-(-)-α-Methylhistamine dihydrobromide (e.g., 6.3 mg/kg) decreases the steady-state levels of tele-methylhistamine (t-MH), a primary histamine metabolite, without changing total histamine levels. This indicates an inhibition of histamine turnover. In a rat model of anesthesia-induced amnesia, pretreatment with 10 mg/kg (i.p.) reverses memory retention deficits caused by Propofol [2][3][4].