A histamine H1 antagonist
Chlorcyclizine is a phenylpiperazine that acts as a histamine H1 receptor antagonist (Ki = 9 nM).1 It has also been shown to be effective against hepatitis C virus (HCV; EC50 = 44 nM in vitro), preventing viral entry into host cells.2 In chimeric mice engrafted with primary human hepatocytes, 10-50 mg/kg chlorcyclizine significantly inhibited infection of HCV genotypes 1b and 2a.2
1.Tran, V.T., Chang, R.S.L., and Snyder, S.H.Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramineProc. Natl. Acad. Sci. USA75(12)6290-6294(1978) 2.He, S., Xiao, J., Dulcey, A.E., et al.Discovery, optimization, and characterization of novel chlorcyclizine derivatives for the treatment of hepatitis C virus infectionJ. Med. Chem.59(3)841-853(2016)
Rats[1]Timed-mated CRL:CD [SD] female rats between 9 and 13 weeks of age at initiation of dosing and weighing between 245 and 363 g are used. Rats are administered a single daily oral gavage dose of 30, 60, or 90 mg/kg Chlorcyclizine (n=8/group) during the sensitive period for palate development, GDs 11 to 14. These doses are selected such that 30 mg/kg is a likely no-effect dose and higher doses of 60 and/or 90 mg/kg will induce a moderate or high incidence of fetal cleft palate. Given that CRL:CDs [SD] rats have an extremely low incidence of spontaneous cleft palate in the testing laboratory, as well as to avoid unnecessary use of animals, a methylcellulose control group is omitted[1].
[1]. Enright BP, et al. Effects of the histamine H1 antagonist Chlorcyclizine on rat fetal palate development. Birth Defects Res B Dev Reprod Toxicol. 2010 Dec;89(6):474-84.
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