Dicycloverine

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Dicycloverine, also known as dicyclomine, sold under the brand name Bentyl among others, is a medication that is used to treat spasms of the intestines such as those that occur in irritable bowel syndrome (IBS).<ref name="BNF76">Template:Cite book</ref><ref name="AHFS2019" /> It is taken by mouth or by injection into a muscle.<ref name=AHFS2019/> While it has been used in baby colic and enterocolitis, evidence does not support these uses.<ref name=AHFS2019/>

Common side effects include dry mouth, blurred vision, weakness, sleepiness, and lightheadedness.<ref name=AHFS2019/> Serious side effects may include psychosis and breathing problems in babies.<ref name=AHFS2019/> Use in pregnancy appears to be safe while use during breastfeeding is not recommended.<ref name=Preg2019>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> How it works is not entirely clear.<ref name=AHFS2019>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Dicycloverine was approved for medical use in the United States in 1950.<ref name=AHFS2019/> It is available as a generic medication.<ref name=BNF76/> In 2022, it was the 176th most commonly prescribed medication in the United States, with more than 2Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

Irritable bowel syndrome

Dicycloverine is used to treat the symptoms of irritable bowel syndrome, specifically hypermotility, in adults.<ref name="CADTH2015">Template:Cite journal</ref><ref name="mono">Template:Cite book</ref> As of 2016, clinical guidelines recommended dicycloverine and other antispasmodics for IBS with diarrhea as a first line treatment.<ref name="CADTH2015" />

Anxiety

Dicycloverine can also be helpful for the treatment of anxiety, but this is an off-label use.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<ref name="mono" />

It should not be given to children or infants with colic due to the risks of convulsions, difficult breathing, irritability, and restlessness,<ref name="WHO" /> and there is little evidence to support the efficacy in such use in any case.<ref>Template:Cite journal Template:Open access</ref>

Dicycloverine is known to impair thinking and coordination.<ref name="mono" />

The effect on the baby during pregnancy or breastfeeding is not well understood.<ref name="mono" />

Adverse effects

Dicycloverine can cause a range of anticholinergic side effects such as dry mouth, nausea, blurred vision, dizziness, confusion, severe constipation, stomach pain, heart palpitations, difficulty urinating, and seizures.<ref name="CADTH2015" />

Pharmacology

Pharmacodynamics

Dicycloverine is a selective muscarinic acetylcholine M₁ receptor antagonist.<ref name="GiachettiGIraldoLadinsky1986">Template:Cite journal</ref> It blocks the action of acetylcholine on muscarinic receptors on smooth muscles in the gastrointestinal tract, relaxing the smooth muscle.<ref name="CADTH2015" />

History

File:Dicyclomine Hydrochloride 10 MG Oral Capsule.jpg

A 10-mg oral capsule of dicyclomine hydrochloride

Dicycloverine was first synthesized chemically in the United States circa 1945 by scientists at William S. Merrell Company.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

It was first marketed in 1952 for gastrointestinal disorders, including colic in infants.<ref name=WHO/> The INN name "dicycloverine" was recommended in 1959.<ref>Template:Cite journal</ref> It was included in the combination drug for morning sickness called Bendectin, along with doxylamine 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, which Merrell had also marketed in the US and Canada.<ref>Template:Cite journal</ref>

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.<ref name="WHO">Template:Cite book</ref>

In 1994, the US Federal Trade Commission 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 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. 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.<ref>Template:Cite journal</ref>

Society and culture

Rarely, there have been reports of dicycloverine abuse. Dicycloverine is an antagonist at σ₁<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and 5-HT_2A<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> receptor sites, though its affinities for these targets are roughly one-fifth to one-tenth as strong as its affinities for CHRM1<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and CHRM4<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> (its clinical targets). It is also a relatively non-polar tertiary amine, able to cross the blood–brain barrier, leading to delirium at high concentrations.<ref name="CADTH2015" /><ref>Template:Cite journal</ref>

External links

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