Loperamide hydrochloride

Loperamide is an opiate which potently and selectively activates μ opioid receptors (K_i = 0.16 nM) exclusively in the periphery. Loperamide is an opiate which potently and selectively activates μ opioid receptors (K_i = 0.16 nM) exclusively in the periphery.^1,2 It is a much weaker agonist of the δ opioid receptor (K_i = 50 nM).¹ Through its actions in the gut wall, loperamide has antidiarrheal action by increasing transit time and by altering intestinal transport of water and electrolytes.^2,3 It also blocks voltage-sensitive sodium channels (IC₅₀ = 270 nM) and high voltage-activated calcium channels (IC₅₀ = 900 nM), presumably through an inhibitory effect on calmodulin.^4,5,2 Loperamide is comparable to morphine in blocking peripheral pain in rats.⁶

1.Breslin, H.J., Miskowski, T.A., Rafferty, B.M., et al.Rationale, design, and synthesis of novel phenyl imidazoles as opioid receptor agonists for gastrointestinal disordersJ. Med. Chem.47(21)5009-5020(2004) 2.Regnard, C., Twycross, R., Mihalyo, M., et al.LoperamideJ. Pain Symptom Manage.42(2)319-323(2011) 3.Trinkley, K.E., and Nahata, M.C.Treatment of irritable bowel syndromeJ. Clin. Pharm. Ther.36(3)275-282(2011) 4.McNeal, E.T., Lewandowski, G.A., Daly, J.W., et al.[3H]Batrachotoxinin A 20α-benzoate binding to voltage-sensitive sodium channels: A rapid and quantitative assay for local anesthetic activity in a variety of drugsJ. Med. Chem.28(3)381-388(1985) 5.Church, J., Fletcher, E.J., Abdel-Hamid, K., et al.Loperamide blocks high-voltage-activated calcium channels and N-methyl-D-aspartate-evoked responses in rat and mouse cultured hippocampal pyramidal neuronsMol. Pharmacol.45747-757(1994) 6.Shannon, H.E., and Lutz, E.A.Comparison of the peripheral and central effects of the opioid agonists loperamide and morphine in the formalin test in ratsNeuropharmacology42(2)253-261(2002)