Background:

Mepyramine maleate, a first generation antihistamine, is an antagonist of histamine H1 receptor, with Kds of 0.8 nM, 5200 nM and >3000 nM for H1, H2, and H3 receptor, respectively, and a pKd of 9.4 for H1 receptor.

Kd: 0.8 nM (Histamine H1 receptor), 5200 nM (Histamine H2 receptor), >3000 nM (Histamine H3 receptor)[1] pKd: 9.4 (Histamine H1 receptor)[2]

Mepyramine maleate is an antagonist of histamine H1 receptor, with Kds of 0.8 nM, 5200 nM and >3000 nM for H1, H2, and H3 receptor, respectively[1], and a pKd of 9.4 for H1 receptor[2]. Mepyramine binds to the H1 receptor with different Kds in Guinea pig brain (0.8 nM), rat brain (9.1 nM) and DDT1-MF-2 and BC3H1 cell (276 nM)[1]. Mepyramine decreases the InsP levels in CHO-gpH1 cells, with log EC50 of -7.94 ± 0.11, and reduces the the maximal response to ATP in CHO-gpH1 cells[3].

Mepyramine obviously decreases the second phase of nociceptive response via i.p at 10 and 20 mg/kg, but shows no significant effect at 5 mg/kg in rats[4].

Reference：
[1]. Hill SJ. Distribution, properties, and functional characteristics of three classes of histamine receptor. Pharmacol Rev. 1990 Mar;42(1):45-83.
[2]. van der Goot H1, et al. Selective ligands as tools to study histamine receptors. Eur J Med Chem. 2000 Jan;35(1):5-20.
[3]. Fitzsimons CP, et al. Mepyramine, a histamine H1 receptor inverse agonist, binds preferentially to a G protein-coupled form of the receptor and sequesters G protein. J Biol Chem. 2004 Aug 13;279(33):34431-9.
[4]. Mojtahedin A, et al. Effects of mepyramine and famotidine on the physostigmine-induced antinociception in the formalin test in rats. Pak J Biol Sci. 2008 Nov 15;11(22):2573-8.