Clemastine (fumarate)

Clemastine (HS-592; Meclastine) fumarate is an orally active, blood-brain barrier-permeable H1 histamine receptor (H1 histamine receptor) antagonist with potent antiallergic effects. Clemastine fumarate also antagonizes muscarinic acetylcholine receptors (mAChR), particularly the M1 and M4 subtypes. In addition to antihistamine effects, Clemastine fumarate exhibits multiple pharmacological activities, especially in promoting central nervous system remyelination, activating autophagy and pyroptosis, exerting anti-apoptotic and neuroprotective effects, and suppressing inflammation ^{[1][2][3][4][5][6]}. IC50 & Target:Histamine H1 Receptor^[1] In Vitro:Clemastine (fumarate) (HS-592 (fumarate)) inhibits histamine induced rise in [Ca²⁺]i in HL-60 cells with an IC₅₀ of 3 nM as compared with that of chlorpheniramine or diphenhydramine with IC₅₀ values of 20 nM and 100 nM, respectively^[1]. Clemastine showed a first-pass reduction in the extent of absorption, with oral bioavailability calculated as 39.2 +/- 12.4%. Extravascular distribution of drug was suggested by the high volume of distribution (799 +/- 315 L) and low Cmax (0.577 +/- 0.252 ng/mL/mg) observed at 4.77 +/- 2.26 hours after administration, and by the biphasic decline in plasma concentration. The terminal elimination half-life (t1/2) of clemastine was 21.3 +/- 11.6 hours. Steady-state concentrations of clemastine were consistent with linear pharmacokinetic processes, and clearance was unaffected by age in the range studied, or by race^[2].