Doxepin-13C-d3 is intended for use as an internal standard for the quantification of doxepin by GC- or LC-MS. Doxepin is a tricyclic antidepressant that binds to the serotonin (5-HT) transporter (SERT) and norepinephrine transporter (NET; Kds = 68 and 29.5 nM, respectively).1 It is a histamine H1 receptor antagonist (Ki = 1.23 nM).2 Doxepin selectively binds to SERT and NET over the dopamine transporter (DAT; Kd = 12,100 nM) and inhibits histamine H1 over H2, H3, and H4 receptors (Kis = 170, 39,810, and 15,135 nM, respectively).1,2 It also binds to the 5-HT2 receptor, as well as to muscarinic acetylcholine and α1-adrenergic receptors (α1-ARs; Kds = 27, 23, and 23.5 nM, respectively).3 Doxepin (10 mg/kg, i.p.) decreases allodynia and hyperalgesia in a mouse model of chronic constriction injury-induced neuropathic pain.4 It increases the distance traveled in the center of the open field test and reduces immobility time in the forced swim test in a mouse model of depression induced by chronic stress when administered orally at a dose of 15 mg/kg.5 Formulations containing doxepin have been used in the treatment of depression and insomnia.
1.Tatsumi, M., Groshan, K., Blakely, R.D., et al.Pharmacological profile of antidepressants and related compounds at human monoamine transportersEur. J. Pharmacol.340(2-3)249-258(1997) 2.Appl, H., Holzammer, T., Dove, S., et al.Interactions of recombinant human histamine H1, H2, H3, and H4 receptors with 34 antidepressants and antipsychoticsNaunyn-Schmiedebergs Arch. Pharmacol.385(2)145-170(2012) 3.Cusack, B., Nelson, A., and Richelson, E.Binding of antidepressants to human brain receptors: Focus on newer generation compoundsPsychopharmacology (Berl.)114(4)559-565(1994) 4.Mika, J., Jurga, A.M., Starnowska, J., et al.Effects of chronic doxepin and amitriptyline administration in naÏve mice and in neuropathic pain mice modelNeuroscience29438-50(2015) 5.Kim, Y.R., Park, B.-K., Kim, Y.H., et al.Antidepressant effect of Fraxinus rhynchophylla Hance extract in a mouse model of chronic stress-induced depressionBioMed. Res. Int.8249563(2018)