Dicycloverine

Dicycloverine is used to treat the symptoms of irritable bowel syndrome, specifically hypermotility, in adults.{{cite journal | author = Canadian Agency for Drugs and Technologies in Health | title = Dicyclomine for Gastrointestinal Conditions: A Review of the Clinical Effectiveness, Safety, and Guidelines | journal = CADTH Rapid Response Reports. | date = 3 December 2015 | pmid = 26985553 }}{{cite book |author=AHFS Staff |date=2006 |title=AHFS DI Essentials |chapter=Dicyclomine hydrochloride |location=Bethesda, MD |publisher=American Society of Health-System Pharmacists / drugs.com |chapter-url=https://www.drugs.com/monograph/dicyclomine-hydrochloride.html |access-date=25 November 2018}} As of 2016, clinical guidelines recommended dicycloverine and other antispasmodics for IBS with diarrhea as a first line treatment.

Dicycloverine can also be helpful for the treatment of anxiety, but this is an off-label use.{{cite web |url=https://cabinethealth.com/blogs/journal/dicyclomine-a-potential-treatment-for-anxiety |title=Dicyclomine: A Potential Treatment for Anxiety |date=12 March 2023 }}

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.{{cite journal | vauthors = Biagioli E, Tarasco V, Lingua C, Moja L, Savino F | title = Pain-relieving agents for infantile colic | journal = The Cochrane Database of Systematic Reviews | volume = 2016 | pages = CD009999 | date = September 2016 | issue = 9 | pmid = 27631535 | pmc = 6457752 | doi = 10.1002/14651858.CD009999.pub2 | hdl = 2434/444531 }} {{open access}}

Dicycloverine is known to impair thinking and coordination.

The effect on the baby during pregnancy or breastfeeding is not well understood.

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.

Dicycloverine is a selective muscarinic acetylcholine M₁ receptor antagonist.{{cite journal | vauthors = Giachetti A, Giraldo E, Ladinsky H, Montagna E | title = Binding and functional profiles of the selective M1 muscarinic receptor antagonists trihexyphenidyl and dicyclomine | journal = Br J Pharmacol | volume = 89 | issue = 1 | pages = 83–90 | date = September 1986 | pmid = 2432979 | pmc = 1917044 | doi = 10.1111/j.1476-5381.1986.tb11123.x | url = }} It blocks the action of acetylcholine on muscarinic receptors on smooth muscles in the gastrointestinal tract, relaxing the smooth muscle.

File:Dicyclomine Hydrochloride 10 MG Oral Capsule.jpg

Dicycloverine was first synthesized chemically in the United States circa 1945 by scientists at William S. Merrell Company.{{cite web |title=Dicyclomine |url=https://pubchem.ncbi.nlm.nih.gov/compound/3042#section=Use-and-Manufacturing |publisher=Pubchem |access-date=25 November 2018}}

It was first marketed in 1952 for gastrointestinal disorders, including colic in infants. The INN name "dicycloverine" was recommended in 1959.{{cite journal |title=International Nonproprietary Names for Pharmaceutical Preparations List #3 |journal=WHO Chronicle |date=December 1959 |volume=13 |issue=12 |pages=463–474 |url=https://www.who.int/medicines/publications/druginformation/innlists/RL03.pdf?ua=1 |format=PDF |access-date=25 November 2018}} 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.{{cite journal |last1=Sanders |first1=Joseph |name-list-style=vanc |title=The Bendectin Litigation: A Case Study in the Life Cycle of Mass Torts |journal=Hastings Law Journal |date=January 1992 |volume=43 |issue=2 |page=317 |url=https://repository.uchastings.edu/cgi/viewcontent.cgi?article=3055&context=hastings_law_journal |format=PDF |access-date=25 November 2018}}

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.{{cite book |title=Consolidated List of Products Whose Consumption and/or Sale Have Been Banned, Withdrawn, Severely Restricted or Not Approved by Governments |edition=12 |date=2005 |publisher=World Health Organization |page=106 |url=http://apps.who.int/medicinedocs/documents/s16780e/s16780e.pdf |archive-url=https://web.archive.org/web/20140407083428/http://apps.who.int/medicinedocs/documents/s16780e/s16780e.pdf |url-status=dead |archive-date=7 April 2014 |access-date=25 November 2018}}

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.{{cite journal |last1=Chien |first1=Colleen |name-list-style=vanc |title=Cheap Drugs at What Price to Innovation: Does the Compulsory Licensing of Pharmaceuticals Hurt Innovation? |journal=Berkeley Technology Law Journal |date=2003 |volume=18 |issue=3 |pages=853–907 |jstor=24116860}}

Rarely, there have been reports of dicycloverine abuse. Dicycloverine is an antagonist at σ₁{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/bioassay/625223#sid=103318016|title=Bioactivity for AID 625223 - SID 103318016}} and 5-HT_2A{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/bioassay/625192#sid=103318016§ion=Version|title=Bioactivity for AID 625192 - SID 103318016}} receptor sites, though its affinities for these targets are roughly one-fifth to one-tenth as strong as its affinities for CHRM1{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/bioassay/625151|title=AID 625151 - DRUGMATRIX: Muscarinic M1 radioligand binding (Ligand: [3H] N-Methylscopolamine) - PubChem}} and CHRM4{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/bioassay/625154|title=AID 625154 - DRUGMATRIX: Muscarinic M4 radioligand binding (Ligand: [3H] N-Methylscopolamine) - PubChem}} (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.{{cite journal | vauthors = Das S, Mondal S, Datta A, Bandyopadhyay S | title = A rare case of dicyclomine abuse | journal = Journal of Young Pharmacists | volume = 5 | issue = 3 | pages = 106–7 | date = September 2013 | pmid = 24396252 | pmc = 3812884 | doi = 10.1016/j.jyp.2013.08.004 }}

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