2712455-05-3

Cyproheptadine-d₃ is intended for use as an internal standard for the quantification of cyproheptadine by GC- or LC-MS. Cyproheptadine is an antihistamine with antiserotonergic and anticholinergic activities.¹ It binds to histamine H₁, muscarinic, and serotonin 5-HT₂ receptors (K_is = 0.38, 1.26, and 0.83 nM, respectively, in radioligand binding assays).² Cyproheptadine reduces histamine-induced spasms in isolated guinea pig ileum (IC₇₅ = 0.0014 μg/ml).³ It protects against intravenous histamine diphosphate-induced death with a 50% protective dose (PD₅₀) value of 0.08 mg/kg and delays induction of aerosolized histamine diphosphate-induced coughing (ED_100sec = 0.29 mg/kg) in guinea pigs. Cyproheptadine also inhibits the lysine methyltransferase SET7/9 (IC₅₀ = 1 μM), decreasing the expression of estrogen receptor α (ERα) in MCF-7 cells.⁴ Formulations containing cyproheptadine have been used in the treatment of allergic reactions including rhinitis, conjunctivitis, and urticaria.

1. Greaves, M.W. Antihistamines Dermatol. Clin. 19(1),53-62(2001).
2. Kakiuchi, M., Ohashi, T., Musoh, K., et al. Studies on the novel antiallergic agent HSR-609: Its penetration into the central nervous system in mice and guinea pigs and its selectivity for the histamine H₁-receptor Jpn. J. Pharmacol. 73(4),291-298(1997).
3. Lish, P.M., Robbins, S.I., and Peters, E.L. Specificity of antihistamine drugs and involvement of the adrenergic system in histamine deaths in the guinea pig J. Pharmacol. Exp. Ther. 153(3),538-543(1966).
4. Takemoto, Y., Ito, A., Niwa, H., et al. Identification of cyproheptadine as an inhibitor of SET domain containing lysine methyltransferase 7/9 (Set7/9) that regulates estrogen-dependent transcription J. Med. Chem. 59(8),3650-3660(2016).