Clemastine 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]

• Inhibition of [Ca²⁺]_i

  HL-60 cells are suspended at 1×10⁷ cells/mL in a buffer consisting of 138 mM NaCl, 6 mM KC1, 1 mM MgSO4, 1 mM Na₂HPO₄, 5 mM NaHCO₃, 5.5 mM glucose, and 20 mM HEPES-NaOH, pH 7.4, supplemented with 0.1% (w/v) bovine serum albumin. The dye fura-2/AM is added at a concentration of 4 μM, and cells are incubated for 10 minutes at 37 °C. Thereafter, cells are diluted with the aforementioned buffer to a concentration of 5×10⁶ cells/mL and incubated for 45 minutes at 37 °C. Subsequently, cells are diluted with the aforementioned buffer to a final concentration of 0.5 × 10⁶ cells/mL and centrifuged at 250 g for 10 minutes at 20 °C. Cells are suspended at 1.0 × 10⁶ cells/mL in the aforementioned buffer and kept at 20 °C until measurement. HL-60 cells are used for up to 4 hours after loading with fura-2/AM, and suspended in 2 mL of the aforementioned buffer, using acryl fluorescence cuvettes. HL-60 cells are incubated for 3 minutes at 37 °C, in the presence of 1 mM Ca²⁺ and various concentrations of Clemastine Fumarate, before the addition of histamine (100 μM). Fluorescence is determined at 37 °C, with constant stirring of the cells at 1×10³ rpm, using a Ratio II spectrofluorometer. The basal fluorescence (basal [Ca²⁺]_i) is measured for 1 minute. The basal [Ca²⁺]_i values are subtracted from the corresponding peak [Ca²⁺]_i values, to calculate the increase in [Ca²⁺]_i. The excitation and emission wavelengths are 340 and 500 nm, respectively. The IC50 value is assessed from competitive curve.

• Animal Models

  Male Wistar rats with paw oedema induced by subplantar injection of zymosan and ear oedema induced by croton oil

• Dosages

  5-20 mg/kg

• Administration

  Intraperitoneally