Clemastine (HS-592) fumarate

Clemastine 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] At concentrations of ≥25 μM, Clemastine Fumarate significantly blocks NK and ADCC reactions of lymphocytes against the human erythroleukemia cell line K562 and human B-lymphoblast cell line SB, respectively. ^[2] Clemastine Fumarate inhibits histamine-induced contraction of guinea pig ileum with an IC50 of 231 nM. ^[3] Clemastine Fumarate potently inhibits the HERG K⁺ channel in a concentration-dependent manner in HEK 293 cells stably expressing HERG channels with an IC50 of 12 nM, which can be attenuated by the Y652A or F656A mutation of HERG. ^[4] Clemastine Fumarate significantly potentiates ATP-induced increase in [Ca²⁺]_i in HEKhP2X7 cells not relying on histamine receptor blockage but on sensitizing P2X7 receptor in a concentration-dependent manner with an EC50 of 10 μM, and increases the IL-1β release from LPS-induced human macrophages. ^[5]

Administration of Clemastine Fumarate (5-20 mg/kg) displays significantly inhibitory effect on simultaneously induced zymosan paw oedema and croton oil ear oedema in rats in a dose-dependent manner, with the inhibition of 53.6% and 46.8%, respectively, at the dose of 20 mg/kg, and with ID50 values of 18.0 mg/kg and 20.5 mg/kg, respectively. ^[6] Clemastine Fumarate treatment strongly reduces innate immune responses to Listeria monocytogenes in mice by interfering with the extracellular signal-regulated kinase (ERK)-mediated production of proinflammatory cytokines such as TNF-α and IL-6 surprisingly not dependent on blocking the histamine H1 receptor, leading to significantly higher mortality. ^[7]