Pimozide-d4 is an internal standard for the quantification of pimozide by GC- or LC-MS. Pimozide is a dopamine receptor antagonist (Kis = 2.4, 0.3, and 1.8 nM for D2, D3, and D4 receptors, respectively).1 It also binds to eight additional receptors (Kds = 25-3,100 nM for the human receptors) and inhibits the voltage-gated sodium channel Nav1.2 and the voltage-gated potassium channel Kv11.1 (IC50s = 42 and 340 nM, respectively).2,3,4 Pimozide (0.5, 1, and 2 mg/kg) decreases the number of licks and reduces fluid intake of a sweetened solution in rats.5 It decreases the number of threats and attacks and increases immobility time in the neutral arena aggression test, indicating increased passiveness, in male mice when administered at a dose of 0.75 mg/kg for 10 days.6 Formulations containing pimozide have been used in the treatment of Tourette syndrome.
|1. Burstein, E.S., Ma, J., Wong, S., et al. Intrinsic efficacy of antipsychotics at human D2, D3, and D4 dopamine receptors: Identification of the clozapine metabolite N-desmethylclozapine as a D2/D3 partial agonist. J. Pharmacol. Exp. Ther. 315(3), 1278-1287 (2005).|2. Richelson, E., and Souder, T. Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci. 68(1), 29-39 (2000).|3. Roufos, I., Hay, S., and Schwarz, R.D. A structure-activity relationship study of novel phenylacetamides which are sodium channel blockers. J. Med. Chem. 39(7), 1514-1520 (1996).|4. Lau, J.F., Jeppesen, C.B., Rimvall, K., et al. Ureas with histamine H3-antagonist receptor activity--a new scaffold discovered by lead-hopping from cinnamic acid amides. Bioorg. Med. Chem. Lett. 16(20), 5303-5308 (2006).|5. Xenakis, S., and Sclafani, A. The effects of pimozide on the consumption of a palatable saccharin-glucose solution in the rat. Pharmacol. Biochem. Behav. 15(3), 435-442 (1980).|6. Navarro, J.F., Velasco, R., and Manzaneque, J.M. Acute and subchronic effects of pimozide on isolation-induced aggression in male mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 24(1), 131-142 (2000).