Dicycloverine, also known as dicyclomine, sold under the brand name Bentyl in the US, is a medication that is used to treat
spasm
A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder.
A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle c ...
s of the
intestines
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
such as occur in
irritable bowel syndrome
Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...
.
[ It is taken by mouth or by ]injection into a muscle
Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have l ...
.[ While it has been used in ]baby colic
Baby colic, also known as infantile colic, is defined as episodes of crying for more than three hours a day, for more than three days a week, for three weeks in an otherwise healthy child. Often crying occurs in the evening. It typically does not ...
and enterocolitis
Enterocolitis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon. It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes. Common clinical manif ...
, evidence does not support these uses.[
Common side effects include dry mouth, blurry vision, weakness, sleepiness, and lightheadedness.][ Serious side effects may include ]psychosis
Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
and breathing problems in babies.[ Use in ]pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
appears to be safe while use during breastfeeding
Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
is not recommended. How it works is not entirely clear.
Dicycloverine was approved for medical use in the United States in 1950.[ It is available as a ]generic medication
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
.[ In 2020, it was the 147th most commonly prescribed medication in the United States, with more than 4million prescriptions.
]
Medical uses
Dicyclomine is used to treat the symptoms of irritable bowel syndrome
Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain and or abdominal bloating and changes in the consistency of bowel movements. These symptoms may ...
, specifically hypermotility, in adults.[ ] As of 2016, clinical guidelines recommended dicycloverine and other antispasmodic
An antispasmodic (synonym: spasmolytic) is a pharmaceutical drug or other agent that suppresses muscle spasms.
Smooth muscle spasm
One type of antispasmodics is used for smooth muscle relaxation, especially in tubular organs of the gastrointesti ...
s for IBS with diarrhea as a first line treatment.
Contraindications
This medicine should not be used for people who have an obstructive GI or urinary condition, severe ulcerative colitis, reflux, any unstable cardiac condition, glaucoma, myasthenia gravis, and anyone who is acutely bleeding.
It should not be given to children or infants with colic due to the risks of convulsions, difficult breathing, irritability, and restlessness, and there is little evidence to support the efficacy in such use in any case.
Because dicycloverine is known to impair thinking and coordination, people taking the drug should avoid driving or operating machinery.
The effect on the baby during pregnancy or breastfeeding is not well understood.
Adverse effects
Dicycloverine can cause a range of anticholinergic
Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system.
These agents inhibit the parasympathetic nervous system ...
side effects such as dry mouth, nausea, blurred vision, dizziness, confusion, severe constipation, stomach pain, heart palpitations, difficulty urinating, and seizures.
Pharmacology
Dicycloverine blocks the action of acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
on cholinergic receptors
An acetylcholine receptor (abbreviated AChR) is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.
Classification
Like other transmembrane receptors, acetylcholine receptors are classified according ...
on smooth muscle
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
s in the GI tract, relaxing the smooth muscle.
History
Dicycloverine was first synthesized chemically in the United States ''circa'' 1945 by scientists at William S. Merrell Company.
It was first marketed in 1952 for gastrointestinal disorders, including colic in infants.[ The INN name "dicycloverine" was recommended in 1959. It was included in the ]combination drug
A combination drug or a fixed-dose combination (FDC) is a medicine that includes two or more active ingredients combined in a single dosage form. Terms like "combination drug" or "combination drug product" can be common shorthand for a FDC prod ...
for morning sickness called Bendectin
Pyridoxine/doxylamine, sold under the brand name Diclectin among others, is a combination of pyridoxine hydrochloride ( vitamin B6) and doxylamine succinate. It is generally used for nausea and vomiting of pregnancy (morning sickness); even thou ...
, along with doxylamine
Doxylamine, sold under the brand name Unisom among others, is an antihistamine medication which is used in the treatment of insomnia and allergies. In combination with pyridoxine ( vitamin B6), it is also used to treat morning sickness in pregna ...
and vitamin B6
Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosphat ...
which was launched in the US 1956; dicyclomine was removed from the formulation in 1976 after Merrell determined that it added no value. Bendectin became the subject of many lawsuits due to allegations that it had caused birth defects similar to thalidomide
Thalidomide, sold under the brand names Contergan and Thalomid among others, is a medication used to treat a number of cancers (including multiple myeloma), graft-versus-host disease, and a number of skin conditions including complications of ...
, which Merrell had also marketed in the US and Canada.
In the mid-1980s several governments restricted its use in infants due to reports of convulsions, difficult breathing, irritability, and restlessness in infants given the drug.
In 1994 the US Federal Trade Commission
The Federal Trade Commission (FTC) is an independent agency of the United States government whose principal mission is the enforcement of civil (non-criminal) antitrust law and the promotion of consumer protection. The FTC shares jurisdiction ov ...
ordered Marion Merrell Dow
Marion Merrell Dow and its predecessor Marion Laboratories was a U.S. pharmaceutical company based in Kansas City, Missouri from 1950 until 1996.
The company specialized in bringing to market drugs that had been discovered but unmarketed by other ...
, which had recently acquired Rugby Darby, the only generic manufacturer of dicycloverine in the US, to promise to grant licenses to its intellectual property on the drug to any company that wanted it, based on antitrust
Competition law is the field of law that promotes or seeks to maintain market competition by regulating anti-competitive conduct by companies. Competition law is implemented through public and private enforcement. It is also known as antitrust l ...
concerns. The US market for the drug at that time was around $8 million; Dow had 60% of it and Rugby had 40%. The next year, Hoechst Marion Roussel
Hoechst AG () was a German chemicals then life-sciences company that became Aventis Deutschland after its merger with France's Rhône-Poulenc S.A. in 1999. With the new company's 2004 merger with Sanofi-Synthélabo, it became a subsidiary of the ...
, which by that time had acquired the business, granted a license to Endo Pharmaceuticals
Endo International plc is an American Irish-domiciled generics and specialty branded pharmaceutical company that generated over 93% of its 2017 sales from the U.S. healthcare system. While Endo's management, operations, and customers are almost ...
. By 2000 several other generic competitors had started selling the drug. The case was part of the reshaping of the US pharmaceutical market that occurred in the 1990s, to favor generic entry.
Society and culture
Although rarely, there have been reports of dicycloverine abuse. Dicycloverine is an antagonist at sigma-1 and 5-HT2A
The 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor (GPCR). The 5-HT2A receptor is a cell surface receptor, but has several intracellular locations. 5-HT is s ...
receptor sites, though its affinities for these targets are roughly one-fifth to one-tenth as strong as its affinities for CHRM1
The muscarinic acetylcholine receptor M1, also known as the cholinergic receptor, muscarinic 1, is a muscarinic receptor that in humans is encoded by the ''CHRM1'' gene. It is localized to 11q13.
This receptor is found mediating slow EPSP at ...
and CHRM4 (its clinical targets). It is also a relatively non-polar tertiary amine, able to cross the blood-brain barrier, leading to delirium
Delirium (also known as acute confusional state) is an organically caused decline from a previous baseline of mental function that develops over a short period of time, typically hours to days. Delirium is a syndrome encompassing disturbances in ...
at high concentrations. journal = Journal of Young Pharmacists, journal = Journal of Young Pharmacists, journal = Journal of Young Pharmacists, journal = Journal of Young Pharmacists,journal = Journal of Young Pharmacists, journal = Journal of Young Pharmacists, journal = Journal of Young Pharmacists, journal = Journal of Young Pharmacists
References
External links
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{{Portal bar , Medicine
Diethylamino compounds
Antispasmodics
Carboxylate esters
Cyclohexanecarboxylic acids
Muscarinic antagonists
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