(R)-(-)-α-Methylhistamine (dihydrochloride)

(R)-(-)-α-Methylhistamine dihydrochloride is a potent, selective and brain-penetrant agonist of H3 histamine receptor, with a K_d of 50.3 nM^[1][2]. (R)-(-)-α-Methylhistamine dihydrochloride can enhance memory retention, attenuates memory impairment in rats^[3][4][5]. In Vitro: (R)-(-)-α-Methylhistamine dihydrochloride is an H3-agonist that is >10 times as potent as histamine (HA). Its selectivity toward H3-receptors is >1000 times as high as that of HA. (R)-(-)-α-Methylhistamine dihydrochloride has only weak affinities for H1 and H2 receptor with a pK_i=4.8 and <3.5, repectively. (R)-(-)-α-Methylhistamine dihydrochloride displays >200-fold selectivity over H4 receptors^[1][2][3]. In Vivo: Pretreatment with (R)-(-)-α-Methylhistamine dihydrochloride (RAMH; 10 mg/kg; i.p.; 60 min before training) reverses Propofol‐induced (25 mg/kg; i.p.; 30 min before training) memory retention^[5].
(R)-(-)-α-Methylhistamine dihydrochloride (6.3 mg/kg; i.p.) significantly decreases the steady-state t-MH level in the mouse brain, whereas these compounds produced no significant changes in the HA level^[3].