Biological Activity
Nefazodone-d6 (hydrochloride) is intended for use as an internal standard for the quantification of nefazodone by GC- or LC-MS. Nefazodone is a serotonin (5-HT), norepinephrine, and dopamine reuptake inhibitor (SNDRI; Kis = 137, 570, 2,380 nM, respectively, in rat brain synaptosomes).1 It is also an antagonist of 5-HT2A, 5-HT1A, and histamine H1 receptors, as well as α1- and α2-adrenergic receptors (α2-ARs; Kis = 7.1, 52, 30, 5.5, and 84 nM, respectively).2 Nefazodone (100 mg/kg) reduces immobility time in the tail suspension test in gerbils.3 However, it is toxic to isolated human hepatocytes in a cultured sandwich hepatocyte preparation when used at a concentration of 30 μM.4 Formulations containing nefazodone have previously been used in the treatment of depression.
References
1.Carlier, P.R., Lo, M.M.-C., Lo, P.C.-K., et al.Synthesis of a potent wide-spectrum serotonin-, norepinephrine-, dopamine-reuptake inhibitor (SNDRI) and a species-selective dopamine-reuptake inhibitor based on the gamma-amino alcohol functional groupBioorg. Med. Chem. Lett.8(5)487-492(1998)
2.Owens, M.J., Neal, W., Plott, S.J., et al.Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolitesJ. Pharmacol. Exp. Ther.283(3)1305-1322(1997)
3.Varty, G.B., Cohen-Williams, M.E., and Hunter, J.C.The antidepressant-like effects of neurokinin NK1 receptor antagonists in a gerbil tail suspension testBehav. Pharmacol.14(1)87-95(2003)
4.Kostrubsky, S.E., Strom, S.C., Kalgutkar, A.S., et al.Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodoneToxicol. Sci.90(2)451-459(2006)
