View source for Dicycloverine

{{Short description|Antispasmodic agent}}
{{Use dmy dates|date=August 2021}}
{{Infobox drug
| Watchedfields = changed
| class = [[Antimuscarinic]]
| verifiedrevid = 460784129
| image = Dicyclomine.svg
| alt = <!--Clinical data-->
| tradename = Byclomine, Bentyl, Dibent, others
| Drugs.com = {{drugs.com|monograph|dicyclomine-hydrochloride}}
| MedlinePlus = a684007
| DailyMedID = Dicyclomine
| pregnancy_AU = B1
| ATC_prefix = A03
| ATC_suffix = AA07
| legal_AU = S4
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only

<!--Pharmacokinetic data-->| routes_of_administration = [[By mouth]], [[intramuscular injection|intramuscular]]
| protein_bound = >99%
| elimination_half-life = 5 hours

<!--Identifiers-->| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 77-19-0
| PubChem = 3042
| IUPHAR_ligand = 355
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00804
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 2934
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 4KV4X8IF6V
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D07820
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 4514
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1123

<!--Chemical data-->| IUPAC_name = 2-(Diethylamino)ethyl 1-cyclohexylcyclohexane-1-carboxylate
| C = 19
| H = 35
| N = 1
| O = 2
| smiles = O=C(OCCN(CC)CC)C1(CCCCC1)C2CCCCC2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C19H35NO2/c1-3-20(4-2)15-16-22-18(21)19(13-9-6-10-14-19)17-11-7-5-8-12-17/h17H,3-16H2,1-2H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CURUTKGFNZGFSE-UHFFFAOYSA-N
}}

<!-- Definition and medical uses -->
'''Dicycloverine''', also known as '''dicyclomine''', sold under the brand name '''Bentyl''' among others, is a [[medication]] that is used to treat [[spasm]]s of the [[intestines]] such as those that occur in [[irritable bowel syndrome]] (IBS).<ref name="BNF76">{{cite book|title=British national formulary: BNF 76|date=2018|publisher=Pharmaceutical Press|isbn=978-0-85711-338-2|pages=759|edition=76}}</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/>

<!-- Side effects and mechanisms -->
Common side effects include [[dry mouth]], [[blurred vision]], [[weakness]], [[Somnolence|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>{{cite web |title=Dicyclomine Pregnancy and Breastfeeding Warnings|url=https://www.drugs.com/pregnancy/dicyclomine.html |website=Drugs.com |access-date=3 March 2019 |language=en}}</ref> How it works is not entirely clear.<ref name=AHFS2019>{{cite web |title=Dicyclomine Hydrochloride Monograph for Professionals |url=https://www.drugs.com/monograph/dicyclomine-hydrochloride.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=3 March 2019 }}</ref>

<!-- Society and culture -->
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 2023, it was the 192nd most commonly prescribed medication in the United States, with more than 2{{nbsp}}million prescriptions.<ref name="Top 300">{{cite web | title=Top 300 of 2023 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=12 August 2025 | archive-date=12 August 2025 | archive-url=https://web.archive.org/web/20250812130026/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Dicyclomine Drug Usage Statistics, United States, 2013 - 2023 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Dicyclomine | access-date = 20 August 2025 }}</ref>

==Medical uses==
===Irritable bowel syndrome===

Dicycloverine is used to treat the symptoms of [[irritable bowel syndrome]], specifically [[Gastrointestinal physiology#Motility|hypermotility]], in adults.<ref name="CADTH2015">{{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 }}</ref><ref name="mono">{{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}}</ref> As of 2016, clinical guidelines recommended dicycloverine and other [[antispasmodic]]s 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|off-label]] use.<ref>{{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 }}</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>{{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 | article-number = CD009999 | date = September 2016 | issue = 9 | pmid = 27631535 | pmc = 6457752 | doi = 10.1002/14651858.CD009999.pub2 | hdl = 2434/444531 }} {{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 [[binding selectivity|selective]] [[muscarinic acetylcholine receptor|muscarinic acetylcholine]] [[M1 receptor|M<sub>1</sub> receptor]] [[receptor antagonist|antagonist]].<ref name="GiachettiGIraldoLadinsky1986">{{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 = }}</ref> It blocks the action of [[acetylcholine]] on muscarinic receptors on [[smooth muscle]]s in the [[gastrointestinal tract]], relaxing the smooth muscle.<ref name="CADTH2015" />

==History==
[[File:Dicyclomine Hydrochloride 10 MG Oral Capsule.jpg|thumb|A 10-mg oral capsule of dicyclomine hydrochloride]]

Dicycloverine was first [[chemical synthesis|synthesized chemically]] in the United States ''circa'' 1945 by scientists at [[Marion Merrell Dow|William S. Merrell Company]].<ref>{{cite web |title=Dicyclomine |url=https://pubchem.ncbi.nlm.nih.gov/compound/3042#section=Use-and-Manufacturing |publisher=Pubchem |access-date=25 November 2018}}</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>{{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}}</ref> It was included in the [[combination drug]] for morning sickness called [[Bendectin]], along with [[doxylamine]] and [[vitamin B6|vitamin B<sub>6</sub>]] 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>{{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}}</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">{{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 |archive-date=7 April 2014 |access-date=25 November 2018}}</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>{{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}}</ref>

==Society and culture==
Rarely, there have been reports of dicycloverine abuse. Dicycloverine is an antagonist at [[Sigma-1_receptor|σ<sub>1</sub>]]<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/bioassay/625223#sid=103318016|title=Bioactivity for AID 625223 - SID 103318016}}</ref> and [[5-HT2A|5-HT<sub>2A</sub>]]<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/bioassay/625192#sid=103318016&section=Version|title=Bioactivity for AID 625192 - SID 103318016}}</ref> receptor sites, though its affinities for these targets are roughly one-fifth to one-tenth as strong as its affinities for [[Muscarinic_acetylcholine_receptor_M1|CHRM1]]<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/bioassay/625151|title=AID 625151 - DRUGMATRIX: Muscarinic M1 radioligand binding (Ligand: &#91;3H&#93; N-Methylscopolamine) - PubChem}}</ref> and [[Muscarinic_acetylcholine_receptor_M4|CHRM4]]<ref>{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/bioassay/625154|title=AID 625154 - DRUGMATRIX: Muscarinic M4 radioligand binding (Ligand: &#91;3H&#93; N-Methylscopolamine) - PubChem}}</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>{{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 }}</ref>

== References ==
{{Reflist}}

== External links ==
{{Commons category}}

{{Drugs for functional gastrointestinal disorders}}
{{Hallucinogens}}
{{Muscarinic acetylcholine receptor modulators}}
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[[Category:Antispasmodics]]
[[Category:Carboxylate esters]]
[[Category:Cyclohexanecarboxylic acids]]
[[Category:Diethylamino compounds]]
[[Category:M1 receptor antagonists]]
[[Category:M2 receptor antagonists]]
[[Category:M3 receptor antagonists]]
[[Category:M4 receptor antagonists]]
[[Category:M5 receptor antagonists]]
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