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 benzamidesJ. 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 antagonistChem. 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 bloodPharmacol. 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 useDrugs25(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 antagonistsNaunyn Schmiedebergs Arch. Pharmacol.338(2)162-168(1988)