Dicycloverine, also known as dicyclomine, sold under the brand name Bentyl among others, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

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 musc ...

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 tract is the largest of the body's systems, after the cardiovascular system. ...

such as those that occur in

irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating, and changes in the consistency of bowel movements. These symptoms may ...

(IBS). It is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

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 ...

. 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 mani ...

, evidence does not support these uses. Common side effects include

dry mouth Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause. This symptom is very common and is o ...

blurred vision Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details. Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressur ...

weakness Weakness is a symptom of many different medical conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, ...

sleepiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...

, and

lightheadedness Lightheadedness is a common and typically unpleasant sensation of dizziness or a feeling that one may faint. The sensation of lightheadedness can be short-lived, prolonged, or, rarely, recurring. In addition to dizziness, the individual may fee ...

. Serious side effects may include

psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

and breathing problems in babies. Use in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

appears to be safe while use during

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

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 2022, it was the 176th most commonly prescribed medication in the United States, with more than 2million prescriptions.

Medical uses

Irritable bowel syndrome

Dicycloverine is used to treat the symptoms of

, 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 gastrointestina ...

s for IBS with diarrhea as a first line treatment.

Anxiety

Dicycloverine can also be helpful for the treatment of

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

, but this is an

off-label Off-label use is the use of pharmaceutical drugs for an unapproved indication (medicine), indication or in an unapproved age group, dose (biochemistry), dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) ca ...

use.

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. Dicycloverine is known to impair thinking and coordination. 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 acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

side effects such as dry mouth, nausea, blurred vision, dizziness, confusion, severe constipation, stomach pain, heart palpitations, difficulty urinating, and seizures.

Pharmacology

Pharmacodynamics

Dicycloverine is a selective muscarinic acetylcholine M₁ receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain. It blocks the action of

acetylcholine Acetylcholine (ACh) is an organic compound 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. Par ...

on muscarinic receptors on

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

s in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

, relaxing the smooth muscle.

History

Dicyclomine Hydrochloride 10 MG Oral Capsule

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 is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...

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 tho ...

, along with

doxylamine Doxylamine is an antihistamine medication used to treat insomnia and allergies, and—in combination with pyridoxine ( vitamin B6)—to treat morning sickness in pregnant women. It is available over-the-counter and is sold under such brand names ...

and vitamin B₆ which was launched in the US in 1956; dicycloverine 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 an oral administered medication used to treat a number of cancers (e.g., multiple myeloma), graft-versus-host disease, and many skin disorders (e.g., complication ...

, which Merrell had also marketed in the US and Canada. In the 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) United States antitrust law, antitrust law and the promotion of consumer protection. It ...

ordered Marion Merrell Dow, which had 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 medication at that time was around $8 million; Dow had 60% of it and Rugby had 40%. The next year, Hoechst Marion Roussel, 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 e ...

. By 2000 several other generic competitors had started selling the medication. The case was part of the reshaping of the US pharmaceutical market that occurred in the 1990s, to favor generic entry.

Society and culture

Rarely, there have been reports of dicycloverine abuse. Dicycloverine is an antagonist at σ₁ and 5-HT_2A 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 The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

, leading to

delirium Delirium (formerly acute confusional state, an ambiguous term that is now discouraged) is a specific state of acute confusion attributable to the direct physiological consequence of a medical condition, effects of a psychoactive substance, or ...

at high concentrations.

References

External links

{{Portal bar , Medicine Antispasmodics Carboxylate esters Cyclohexanecarboxylic acids Diethylamino compounds M1 receptor antagonists M2 receptor antagonists M3 receptor antagonists M4 receptor antagonists M5 receptor antagonists Wikipedia medicine articles ready to translate