Clemastine fumarate

2 years -80 in solvent

Intraperitoneally

Currently under Phase III study to evaluate the effectiveness of Clemastine Fumarate 1.0 mg/g + dexamethasone 0.5 mg/g compared to dexchlorpheniramine maleate 10 mg/g in eczema treatment

Dissolved in saline

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 uM, 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 uM, and increases the IL-1beta release from LPS-induced human macrophages. [5]

Inhibition of [Ca2+]i, HL-60 cells are suspended at 1107 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 uM, and cells are incubated for 10 minutes at 37 C. Thereafter, cells are diluted with the aforementioned buffer to a concentration of 5106 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 uM). Fluorescence is determined at 37 C, with constant stirring of the cells at 1103 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.

Clemastine fumarate is a selective histamine H1 receptor antagonist with IC50 of 3 nM. Clemastine stimulates autophagy via mTOR pathway.