Open Access Open Access  Restricted Access Subscription or Fee Access

Loperamide: From antidiarrheal to analgesic

Rakesh Kumar, MSc, PhD


Loperamide, an antidiarrheal drug has been observed to produce analgesia in animal models of pain. However, the exact mechanism underlying loperamide analgesia needs further studies.


loperamide, analgesia, animal models of pain

Full Text:



Niemegeers CJE, Lenaerts FM, Janssen PAJ: Loperamide, a novel type of antidiarrheal agent. Drug Res. 1974; 24: 1633-1653.

DeHaven-Hudkins DL, Burgos LC, Cassel JA, et al.: Loperamide (ADL 2-1294), an opioid antihyperalgesic agent with peripheral selectivity. J Pharmacol Exp Ther. 1999; 289: 494-502.

Sasaki A, Nakashima Y, Takasaki I, et al.: Effects of loperamide on mechanical allodynia induced by herpes simplex virus type- 1 in mice. J Pharmacol Sci. 2007; 104: 218-224.

Guan Y, Johanek LM, Hartke TV, et al.: Peripherally acting mu-opioid receptor agonist attenuates neuropathic pain in rats after L5 spinal nerve injury. Pain. 2008; 138: 318-329.

Ringkamp M, Tal M, Hartke TV, et al.: Local loperamide injection reduces mechanosensitivity of rat cutaneous, nociceptive C-fibers. PLoS One 2012; 7(7): e42105.

Hagiwara K, Nakagawasai O, Murata A, et al.: Analgesic action of loperamide, an opioid agonist, and its blocking action on voltage-dependent Ca2+ channels. Neurosci Res. 2003; 46: 493-497.

Shannon HE, Lutz EA: Comparison of the peripheral and central effects of the opioid agonists loperamide and morphine in the formalin test in rats. Neuropharmacol. 2002; 42: 253-261.

Ray SB, Verma D, Wadhwa S: Acute analgesic effect of loperamide as compared to morphine after intrathecal administration in rat. Indian J Exp Biol. 2005; 43: 425-429.

Ray SB, Yaksh TL: Spinal antinociceptive action of loperamide is mediated by opioid receptors in the formalin test in rats. Neurosci Lett. 2008; 448: 260-262.

Kumar R, Reeta KH, Ray SB: Antinociceptive effect of intrathecal loperamide: Role of mu-opioid receptor and calcium channels. Eur J Pharmacol. 2012; 696(1-3): 77.

Choo EF, Kurnik D, Muszkat M, et al.: Differential in vivo sensitivity to inhibition of P-glycoprotein located in lymphocytes, testes, and the blood-brain barrier. J Pharmacol Exp Ther. 2006; 317: 1012-1018.

Yanagita T, Miyasato K, Sato J: Dependence potential of loperamide studied in rhesus monkeys. NIDA Res Monogr. 1979; 27: 106-113.

Nakamura H, Ishii K, Yokoyama Y. et al.: Physical Dependence on Loperamide Hydrochloride in Mice and Rats (in Japanese). Yakugaku Zasshi. 1982; 102(11): 1074-1085.

Bichner F (ed.): Australian Medicine Handbook. Adelaide: Australian Medicine Handbook Pty Ltd ed., 2010.

Rathmell JP, Lair TR, Nauman B: The role of intrathecal drugs in the treatment of acute pain. Anesth Analg. 2005; 101: S30-S43.

Dalwadi G, Sunderland B: An ion pairing approach to increase the loading of hydrophilic and lipophilic drugs into PEGylated PLGA nanoparticles. Eur J Pharm Biopharm. 2009; 71: 231-242.



  • There are currently no refbacks.