Metoclopramide-d3

Metoclopramide-d3 is intended for use as an internal standard for the quantification of metoclopramide by GC- or LC-MS. Metoclopramide is an orally bioavailable serotonin (5-HT) receptor 5-HT3 antagonist with Ki and IC50 values of 995 and 308 nM, respectively, in rat cortical membranes.1,2 It is also a dopamine D2 receptor antagonist (IC50 = 483 nM in rat brain synaptic membranes).2 Oral administration of metoclopramide inhibits emesis induced by cisplatin and apomorphine in ferrets and dogs with ED50 values of 6.17 and 0.45 mg/kg, respectively.1,2 Metoclopramide reversibly inhibits human acetylcholinesterase (AChE) isolated from the caudate nucleus (Kis = 9.3 and 82 μM for competitive and non-competitive inhibition, respectively).3 Formulations containing metoclopramide have been used as anti-emetic and antipsychotic agents.4,5

|1. Youssefyeh, R.D., Campbell, H.F., Klein, S., et al. Development of high-affinity 5-HT3 receptor antagonists. 1. Initial structure-activity relationship of novel benzamides. J. Med. Chem. 35(5), 895-903 (1992).|2. Hirokawa, Y., Harada, H., Yoshikawa, T., et al. Synthesis and structure-activity relationships of 4-amino-5-chloro-N-(1,4-dialkylhexahydro-1,4-diazepin-6-yl)-2-methoxybenzamide derivatives, novel and potent serotonin 5-HT3 and dopamine D2 receptors dual antagonist. Chem. Pharm. Bull. (Tokyo) 50(7), 941-959 (2002).|3. Chemnitius, J.M., Haselmeyer, K.H., Gonska, B.D., et al. Indirect parasympathomimetic activity of metoclopramide: Reversible inhibition of cholinesterases from human central nervous system and blood. Pharmacol. Res. 34(1-2), 65-72 (1996).|4. Harrington, R.A., Hamilton, C.W., Brogden, R.N., et al. Metoclopramide. An updated review of its pharmacological properties and clinical use. Drugs 25(5), 451-494 (1983).|5. Altar, C.A., Boyar, W.C., Wasley, A., et al. Dopamine neurochemical profile of atypical antipsychotics resembles that of D-1 antagonists. Naunyn Schmiedebergs Arch. Pharmacol. 338(2), 162-168 (1988).