TD-4208

TD-4208 is an antagonist of muscarinic acetylcholine receptors (mAChRs; K_is = 0.42, 0.3, 0.18, and 0.55 nM for M₁, M₂, M₃, and M₄ receptors, respectively, in membranes from CHO-K1 cells expressing the human receptors).¹ It is selective for these receptors over M₅ muscarinic receptors (K_i = 6.31 nM in membranes from CHO-K1 cells expressing the human receptor). TD-4208 inhibits calcium mobilization induced by acetylcholine (AChE; Item No. 23829) in CHO-K1 cells expressing M₂ and M₃ muscarinic receptors. It decreases AChE-induced contractions in isolated rat trachea in a concentration-dependent manner. TD-4208 decreases AChE-induced bronchoconstriction and reduces salivation induced by pilocarpine, a surrogate test for noisy breathing, in rats (ID₅₀s = 45 and 1,164 µg/ml, respectively).² It also decreases AChE-induced bronchoconstriction in dogs when administered intranasally at doses of 10 and 30 µg/kg. Formulations containing TD-4208 have been used in the treatment of chronic obstructive pulmonary disease (COPD).

WARNING This product is not for human or veterinary use.

1. Hegde, S.S., Pulido-Rios, M.T., Luttmann, M.A., et al. Pharmacological properties of revefenacin (TD-4208), a novel, nebulized long-acting, and lung selective muscarinic antagonist, at human recombinant muscarinic receptors and in rat, guinea pig, and human isolated airway tissues. Pharmacol. Res. Perspect. 6(3), e00400 (2018).

2. Pulido-Rios, M.T., McNamara, A., Obedencio, G.P., et al. In vivo pharmacological characterization of TD-4208, a novel lung-selective inhaled muscarinic antagonist with sustained bronchoprotective effect in experimental animal models. J. Pharmacol. Exp. Ther. 346(2), 241-250 (2103).