Desloratadine-3,3,5,5-d4

Description

Desloratadine-d₄ is intended for use as an internal standard for the quantification of desloratadine by GC- or LC-MS. Desloratadine is a histamine H₁ receptor antagonist (K_i = 0.97 nM) and an active metabolite of loratadine .^1,2 It is formed from loratadine primarily by the cytochrome P450 (CYP) isoforms CYP3A4, CYP2D6, and CYP2C19.³ It also inhibits calcium flow in neurons and glia in vitro (IC₅₀s = 9.177 and 0.3185 μM, respectively), an effect that can be blocked by knockdown of the 5-HT receptor subtype 5-HT_2A.⁴ Desloratadine (10 mg/kg) reduces ovalbumin-induced sneezing, nose rubbing, eye watering, and congestion in ovalbumin-sensitized guinea pigs.⁵ It also increases the clearance of amyloid-β by microglia and reverses learning and memory deficits in the Morris water maze in the transgenic APP/PS1 mouse model of Alzheimer’s disease when administered at a dose of 20 mg/kg per day.⁴ Formulations containing desloratadine have been used in the treatment of seasonal and perennial allergic rhinitis and chronic idiopathic urticaria.

References

1. Lewis, T.A., Young, M.A., Arrington, M.P., et al. Cetirizine and loratadine-based antihistamines with 5-lipoxygenase inhibitory activity Bioorg. Med. Chem. Lett. 14(22),5591-5594(2004).
2. Ramanathan, R., Alvarez, N., Su, A.-D., et al. Metabolism and excretion of loratadine in male and female mice, rats and monkeys Xenobiotica 35(2),155-189(2005).
3. Aratyn-Schaus, Y., and Ramanathan, R. Advances in high-resolution MS and hepatocyte models solve a long-standing metabolism challenge: The loratadine story Bioanalysis 8(16),1645-1662(2016).
4. Lu, J., Zhang, C., Lv, J., et al. Antiallergic drug desloratadine as a selective antagonist of 5HT2A receptor ameliorates pathology of Alzheimer’s disease model mice by improving microglial dysfunction Aging Cell 20(1),e13286(2021).
5. Bahekar, P.C., Shah, J.H., Ayer, U.B., et al. Validation of guinea pig model of allergic rhinitis by oral and topical drugs Int. Immunopharmacol. 8(11),1540-1551(2008).