Dicycloverine,also known asdicyclomine,sold under the brand nameBentylamong others, is amedicationthat is used to treatspasmsof theintestinessuch as those that occur inirritable bowel syndrome(IBS).[1][2]It is takenby mouthor byinjection into a muscle.[2]While it has been used inbaby colicandenterocolitis,evidence does not support these uses.[2]
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| Trade names | Byclomine, Bentyl, Dibent, others |
| AHFS/Drugs | Monograph |
| MedlinePlus | a684007 |
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| Routes of administration | By mouth,intramuscular |
| Drug class | Antimuscarinic |
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| Pharmacokineticdata | |
| Protein binding | >99% |
| Eliminationhalf-life | 5 hours |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.000.919 |
| Chemical and physical data | |
| Formula | C19H35NO2 |
| Molar mass | 309.494g·mol−1 |
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Common side effects includedry mouth,blurred vision,weakness,sleepiness,andlightheadedness.[2]Serious side effects may includepsychosisand breathing problems in babies.[2]Use inpregnancyappears to be safe while use duringbreastfeedingis not recommended.[3]How it works is not entirely clear.[2]
Dicycloverine was approved for medical use in the United States in 1950.[2]It is available as ageneric medication.[1]In 2022, it was the 176th most commonly prescribed medication in the United States, with more than 2million prescriptions.[4][5]
Medical uses
editIrritable bowel syndrome
editDicycloverine is used to treat the symptoms ofirritable bowel syndrome,specificallyhypermotility,in adults.[6][7]As of 2016, clinical guidelines recommended dicycloverine and otherantispasmodicsfor IBS with diarrhea as a first line treatment.[6]
Anxiety
editDicycloverine can also be helpful for the treatment ofanxiety,but this is anoff-labeluse.[8]
Contraindications
editThis 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.[7]
It should not be given to children or infants with colic due to the risks of convulsions, difficult breathing, irritability, and restlessness,[9]and there is little evidence to support the efficacy in such use in any case.[10]
Dicycloverine is known to impair thinking and coordination.[7]
The effect on the baby during pregnancy or breastfeeding is not well understood.[7]
Adverse effects
editDicycloverine can cause a range ofanticholinergicside effects such as dry mouth, nausea, blurred vision, dizziness, confusion, severe constipation, stomach pain, heart palpitations, difficulty urinating, and seizures.[6]
Pharmacology
editPharmacodynamics
editDicycloverine is aselectivemuscarinic acetylcholineM1receptorantagonist.[11]It blocks the action ofacetylcholineon muscarinic receptors onsmooth musclesin thegastrointestinal tract,rela xing the smooth muscle.[6]
History
edit
Dicycloverine was firstsynthesized chemicallyin the United Statescirca1945 by scientists atWilliam S. Merrell Company.[12]
It was first marketed in 1952 for gastrointestinal disorders, including colic in infants.[9]The INN name "dicycloverine" was recommended in 1959.[13]It was included in thecombination drugfor morning sickness calledBendectin,along withdoxylamineandvitamin B6which 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 tothalidomide,which Merrell had also marketed in the US and Canada.[14]
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.[9]
In 1994, the USFederal Trade CommissionorderedMarion 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 onantitrustconcerns. 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 toEndo 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.[15]
Society and culture
editRarely, there have been reports of dicycloverine abuse. Dicycloverine is an antagonist atσ1[16]and5-HT2A[17]receptor sites, though its affinities for these targets are roughly one-fifth to one-tenth as strong as its affinities forCHRM1[18]andCHRM4[19](its clinical targets). It is also a relatively non-polar tertiary amine, able to cross theblood–brain barrier,leading todeliriumat high concentrations.[6][20]
References
edit- ^abBritish national formulary: BNF 76(76 ed.). Pharmaceutical Press. 2018. p. 759.ISBN9780857113382.
- ^abcdefg"Dicyclomine Hydrochloride Monograph for Professionals".Drugs.American Society of Health-System Pharmacists.Retrieved3 March2019.
- ^"Dicyclomine Pregnancy and Breastfeeding Warnings".Drugs.Retrieved3 March2019.
- ^"The Top 300 of 2022".ClinCalc.Archivedfrom the original on 30 August 2024.Retrieved30 August2024.
- ^"Dicyclomine Drug Usage Statistics, United States, 2013 - 2022".ClinCalc.Retrieved30 August2024.
- ^abcdeCanadian Agency for Drugs and Technologies in Health (3 December 2015). "Dicyclomine for Gastrointestinal Conditions: A Review of the Clinical Effectiveness, Safety, and Guidelines".CADTH Rapid Response Reports.PMID26985553.
- ^abcdAHFS Staff (2006)."Dicyclomine hydrochloride".AHFS DI Essentials.Bethesda, MD: American Society of Health-System Pharmacists / drugs.Retrieved25 November2018.
- ^"Dicyclomine: A Potential Treatment for Anxiety".12 March 2023.
- ^abcConsolidated List of Products Whose Consumption and/or Sale Have Been Banned, Withdrawn, Severely Restricted or Not Approved by Governments(PDF)(12 ed.). World Health Organization. 2005. p. 106. Archived fromthe original(PDF)on 7 April 2014.Retrieved25 November2018.
- ^Biagioli E, Tarasco V, Lingua C, Moja L, Savino F (September 2016)."Pain-relieving agents for infantile colic".The Cochrane Database of Systematic Reviews.2016(9): CD009999.doi:10.1002/14651858.CD009999.pub2.hdl:2434/444531.PMC6457752.PMID27631535.
- ^Giachetti A, Giraldo E, Ladinsky H, Montagna E (September 1986)."Binding and functional profiles of the selective M1 muscarinic receptor antagonists trihexyphenidyl and dicyclomine".Br J Pharmacol.89(1): 83–90.doi:10.1111/j.1476-5381.1986.tb11123.x.PMC1917044.PMID2432979.
- ^"Dicyclomine".Pubchem.Retrieved25 November2018.
- ^"International Nonproprietary Names for Pharmaceutical Preparations List #3"(PDF).WHO Chronicle.13(12): 463–474. December 1959.Retrieved25 November2018.
- ^Sanders J (January 1992)."The Bendectin Litigation: A Case Study in the Life Cycle of Mass Torts"(PDF).Hastings Law Journal.43(2): 317.Retrieved25 November2018.
- ^Chien C (2003). "Cheap Drugs at What Price to Innovation: Does the Compulsory Licensing of Pharmaceuticals Hurt Innovation?".Berkeley Technology Law Journal.18(3): 853–907.JSTOR24116860.
- ^"Bioactivity for AID 625223 - SID 103318016".
- ^"Bioactivity for AID 625192 - SID 103318016".
- ^"AID 625151 - DRUGMATRIX: Muscarinic M1 radioligand binding (Ligand: [3H] N-Methylscopolamine) - PubChem".
- ^"AID 625154 - DRUGMATRIX: Muscarinic M4 radioligand binding (Ligand: [3H] N-Methylscopolamine) - PubChem".
- ^Das S, Mondal S, Datta A, Bandyopadhyay S (September 2013)."A rare case of dicyclomine abuse".Journal of Young Pharmacists.5(3): 106–7.doi:10.1016/j.jyp.2013.08.004.PMC3812884.PMID24396252.
External links
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