General Information

Loperamide was discovered by Janssen Pharmaceutica in 1969. It is an extremely effective drug against diarrhea resulting from gastroenteritis and inflammatory bowel disease, as well as acute nonspecific diarrhea. Loperamide is available over-the-counter, the most famous preparation being Imodium AD, a household name. The drug may also be beneficial to withdrawaling opioid addicts because it has been shown to relieve some morphine withdrawal symptoms. ^[1]

Chemical Names.4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidyl]-N,N-dimethyl-2,2-diphenyl-butanamide.
Chemical Formula. C₂₉H₃₃ClN₂O₂
Classification. Opioid.
Primary Uses. Anti-diarrhea, Opioid withdrawal comfort medicine.
Other Names. Imodium AD, Kaopectate II, Maalox Anti-Diarrheal.

Pharmacology and Pharmacokinetics

Loperamide is indicated for the control and symptomatic relief of diarrhea, and also chronic diarrhea associated with inflammatory bowel disease. Loperamide works by reducing bowel motility, lessening the loss of electrolytes and fluids, and increasing fecal volume, viscosity and bulk density. The desired effect, which is in essence, constipation, has not been observed to be affected by tolerance. Loperamide attaches to mu-opioid receptors in the myenteric plexus large intestines, which is where the motility of the smooth muscles on the intestinal wall is decreased, causing the desired effect. It also works as a non-selective calcium channel blocker. Loperamide does not affect the central nervous system like other opioids do, due to its inability to readily cross the blood-brain barrier. The half-life of loperamide ranges from 9.1 to 14.4 hours (average of 10.8 hours). ^[2]

Law

Loperamide is available over-the-counter in the United States. There are no restrictions on age or quantity. When the drug was first introduced, loperamide was briefly classified as a Schedule V substance due to the presence of a physical withdrawal syndrome at the end of a long-term clinical study which used very high doses of the drug. It was quickly unscheduled due to the very, very low abuse potential.

Side Effects

• Abdominal pain or discomfort
• Drowsiness
• Dizziness
• Tiredness
• Dry mouth
• Nausea and vomiting
• Skin rash
• Constipation

Opiate-like effects have been observed in children under three, and it is believed that young children are more sensitive to these effects than adults.

Withdrawal

Loperamide may cause physical dependence, though it is unlikely unless high doses are being used over a long period of time. Clinical trials have indicated it can cause physical dependency, which resulted in the scheduling of loperamide, though the results were insignificant because it has next to no abuse potential due to its inability to cross the blood-brain barrier.

Additional Information

• How can Imodium AD help during opioid withdrawal?
• Over-the-Counter Comfort Medicine for Opioid Withdrawal
• Opioid Addiction
• Opioids FAQ

Sources

[1] Loperamide - Wikipedia. Wikipedia. 1 June 2007. Accessed: June 5, 2007. [link]
[2] DrugBank: Loperamide . DrugBank. Accession Number: APRD00275. 1 February 2007. Accessed: June 5, 2007. [link]
[3] RxMed: Pharmaceutical Information - IMODIUM. RxMed. Accessed: June 5, 2007. [link]