glycopyrronium bromide
{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox drug
| image = Glycopyrronium bromide.svg
| Verifiedfields = changed
| INN = Glycopyrronium
| verifiedrevid = 461122867
| width =
| alt =
| caption =
| USAN = glycopyrrolate
| pronounce =
| tradename = Robinul, Cuvposa, Seebri, others
| Drugs.com = {{drugs.com|monograph|glycopyrrolate}}
| MedlinePlus = a602014
| DailyMedID = Glycopyrrolate
| pregnancy_AU = B2
| pregnancy_AU_comment =
| pregnancy_category =
| routes_of_administration = By mouth, intravenous, inhalation, topical, injection, subcutaneous
| class = Antimuscarinic (peripherally-selective)
| ATC_prefix = A03
| ATC_suffix = AB02
| ATC_supplemental = {{ATC|D11|AA01}} {{ATC|R03|BB06}}
| legal_AU = S3 / S4
| legal_AU_comment =
| legal_BR =
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = {{cite web | title= Neurological therapies | website=Health Canada | date=9 May 2018 | url=https://www.canada.ca/en/services/health/drug-health-products/drug-medical-device-highlights-2017/approved-drugs/neurological-therapies.html | access-date=13 April 2024}}
| legal_DE =
| legal_DE_comment =
| legal_NZ =
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment = {{cite web | title=Robinul- glycopyrrolate tablet Robinul Forte- glycopyrrolate tablet | website=DailyMed | date=1 June 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94fb029a-6371-4b1c-89de-35e8209c7cab | access-date=20 June 2022}}{{cite web | title=Dartisla ODT- glycopyrrolate orally disintegrating tablets tablet, orally disintegrating | website=DailyMed | date=9 December 2021 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=52daf47e-7ba3-4105-be7f-27001a87e16e | access-date=20 June 2022}}
| legal_EU = Rx-only
| legal_EU_comment = {{cite web | title=Sialanar EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/sialanar | access-date=29 January 2023}} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
| legal_UN =
| legal_UN_comment =
| legal_status = Rx-only
| bioavailability =
| protein_bound =
| metabolism =
| metabolites =
| onset =
| elimination_half-life = 0.6–1.2 hours
| duration_of_action =
| excretion = 85% Kidney, unknown amount in the bile
| index2_label = as cation
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 51186-83-5
| CAS_number2 = 596-51-0
| CAS_supplemental =
| PubChem = 3494
| PubChem2 = 11693
| IUPHAR_ligand = 7459
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DBSALT001183
| DrugBank2 = DB00986
| ChemSpiderID = 11201
| ChemSpiderID2 = 3374
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = V92SO9WP2I
| UNII2 = A14FB57V1D
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00540
| KEGG2 = D10938
| ChEBI = 90972
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1201027
| ChEMBL2 = 1201335
| NIAID_ChemDB =
| PDB_ligand =
| synonyms =
| IUPAC_name = 3-[2-Cyclopentyl(hydroxy)phenylacetoxy]-1,1-dimethylpyrrolidinium bromide
| C = 19
| H = 28
| Br = 1
| N = 1
| O = 3
| SMILES = C[N+]1(CCC(C1)OC(=O)C(C2CCCC2)(C3=CC=CC=C3)O)C.[Br-]
| SMILES2 = C[N+]1(CCC(C1)OC(=O)C(C2CCCC2)(C3=CC=CC=C3)O)C
| StdInChI = 1S/C19H28NO3.BrH/c1-20(2)13-12-17(14-20)23-18(21)19(22,16-10-6-7-11-16)15-8-4-3-5-9-15;/h3-5,8-9,16-17,22H,6-7,10-14H2,1-2H3;1H/q+1;/p-1
| StdInChI2 = 1S/C19H28NO3/c1-20(2)13-12-17(14-20)23-18(21)19(22,16-10-6-7-11-16)15-8-4-3-5-9-15/h3-5,8-9,16-17,22H,6-7,10-14H2,1-2H3/q+1
| StdInChIKey = VPNYRYCIDCJBOM-UHFFFAOYSA-M
| StdInChIKey2 = ANGKOCUUWGHLCE-UHFFFAOYSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
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| boiling_notes =
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| specific_rotation =
}}
Glycopyrronium bromide is a medication of the muscarinic anticholinergic group. It does not cross the blood–brain barrier and consequently has few to no central effects. It is given by mouth,{{cite web | title=Glycopyrrolate Oral Inhalation | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a618016.html | access-date=20 June 2022 | archive-date=17 August 2021 | archive-url=https://web.archive.org/web/20210817020822/https://medlineplus.gov/druginfo/meds/a618016.html | url-status=live }} via intravenous injection, on the skin,{{cite web | title=Glycopyrronium Topical | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a618046.html | access-date=20 June 2022 | archive-date=17 August 2021 | archive-url=https://web.archive.org/web/20210817175947/https://medlineplus.gov/druginfo/meds/a618046.html | url-status=live }} and via inhalation. It is a synthetic quaternary ammonium compound. The cation, which is the active moiety, is called glycopyrronium (INN){{cite journal | vauthors = Bajaj V, Langtry JA | title = Use of oral glycopyrronium bromide in hyperhidrosis | journal = The British Journal of Dermatology | volume = 157 | issue = 1 | pages = 118–121 | date = July 2007 | pmid = 17459043 | doi = 10.1111/j.1365-2133.2007.07884.x | s2cid = 29080876 }} or glycopyrrolate (USAN).
The most common side effects include irritability, flushing, nasal congestion, reduced secretions in the airways, dry mouth, constipation, diarrhea, nausea and vomiting, and urinary retention.
In September 2012, glycopyrronium was approved for medical use in the European Union. In June 2018, glycopyrronium was approved by the U.S. Food and Drug Administration (FDA) to treat excessive underarm sweating, becoming the first drug developed specifically to reduce excessive sweating.{{Cite news|url=https://apnews.com/21f28f1327ca4f9497cf878cc0229444|title=FDA OKs first drug made to reduce excessive sweating|work=AP News|access-date=2018-07-02|archive-date=2018-07-02|archive-url=https://web.archive.org/web/20180702233319/https://apnews.com/21f28f1327ca4f9497cf878cc0229444|url-status=live}} It is on the World Health Organization's List of Essential Medicines.{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}
Medical uses
Glycopyrronium was first used in 1961 to treat peptic ulcers. Since 1975, intravenous glycopyrronium has been used before surgery to reduce salivary, tracheobronchial, and pharyngeal secretions. It is also used in conjunction with neostigmine, a neuromuscular blocking reversal agent, to prevent neostigmine's muscarinic effects such as bradycardia.{{cite journal | vauthors = Howard J, Wigley J, Rosen G, D'mello J | title = Glycopyrrolate: It's time to review | journal = Journal of Clinical Anesthesia | volume = 36 | pages = 51–53 | date = February 2017 | pmid = 28183573 | doi = 10.1016/j.jclinane.2016.09.013 }} It can be administered to raise the heart rate in reflex bradycardia as a result of a vasovagal reaction, which often will also increase the blood pressure.{{cite book | vauthors = Gallanosa A, Stevens JB, Quick J | chapter = Glycopyrrolate | date = June 2023 | title = StatPearls [Internet] | location = Treasure Island (FL) | publisher = StatPearls Publishing | pmid = 30252291 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK526035/ | access-date=September 13, 2024 }}
It is also used to reduce excessive saliva (sialorrhea),{{cite journal | vauthors = Mier RJ, Bachrach SJ, Lakin RC, Barker T, Childs J, Moran M | title = Treatment of sialorrhea with glycopyrrolate: A double-blind, dose-ranging study | journal = Archives of Pediatrics & Adolescent Medicine | volume = 154 | issue = 12 | pages = 1214–1218 | date = December 2000 | pmid = 11115305 | doi = 10.1001/archpedi.154.12.1214 | url = http://archpedi.ama-assn.org/cgi/pmidlookup?view=long&pmid=11115305 | access-date = 2008-11-26 | url-status = live | doi-access = free | archive-url = https://archive.today/20110810032036/http://archpedi.ama-assn.org/cgi/pmidlookup?view=long&pmid=11115305 | archive-date = 2011-08-10 }}{{cite journal | vauthors = Tscheng DZ | title = Sialorrhea - therapeutic drug options | journal = The Annals of Pharmacotherapy | volume = 36 | issue = 11 | pages = 1785–1790 | date = November 2002 | pmid = 12398577 | doi = 10.1345/aph.1C019 | s2cid = 45799443 }}{{dead link|date=October 2017 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal | vauthors = Olsen AK, Sjøgren P | title = Oral glycopyrrolate alleviates drooling in a patient with tongue cancer | journal = Journal of Pain and Symptom Management | volume = 18 | issue = 4 | pages = 300–302 | date = October 1999 | pmid = 10534970 | doi = 10.1016/S0885-3924(99)00080-9 | doi-access = free }} and to treat Ménière's disease.{{cite journal|title=Medical therapy in Ménière's disease|journal=Audiological Medicine| vauthors = Maria SA, Claudia C, Pamela G, Andrea C, Roberto A |date=1 December 2012|volume=10|issue=4|pages=171–177|doi=10.3109/1651386X.2012.718413|s2cid=72380413}}
It has been used topically and orally to treat hyperhidrosis, in particular, gustatory hyperhidrosis and generalized hyperhidrosis.{{cite journal | vauthors = Kim WO, Kil HK, Yoon DM, Cho MJ | title = Treatment of compensatory gustatory hyperhidrosis with topical glycopyrrolate | journal = Yonsei Medical Journal | volume = 44 | issue = 4 | pages = 579–582 | date = August 2003 | pmid = 12950111 | doi = 10.3349/ymj.2003.44.4.579 | doi-access = free }}{{cite journal | vauthors = Kim WO, Kil HK, Yoon KB, Yoon DM | title = Topical glycopyrrolate for patients with facial hyperhidrosis | journal = The British Journal of Dermatology | volume = 158 | issue = 5 | pages = 1094–1097 | date = May 2008 | pmid = 18294315 | doi = 10.1111/j.1365-2133.2008.08476.x | s2cid = 39870296 }}
When inhaled, it is used to treat chronic obstructive pulmonary disease (COPD).{{cite web | title=Seebri Breezhaler EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/seebri-breezhaler | access-date=28 February 2020 | archive-date=29 February 2020 | archive-url=https://web.archive.org/web/20200229101656/https://www.ema.europa.eu/en/medicines/human/EPAR/seebri-breezhaler | url-status=live }}{{cite web | title=Tovanor Breezhaler EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/tovanor-breezhaler | access-date=28 February 2020 | archive-date=29 February 2020 | archive-url=https://web.archive.org/web/20200229101658/https://www.ema.europa.eu/en/medicines/human/EPAR/tovanor-breezhaler | url-status=live }}{{cite web | title=Enurev Breezhaler EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/enurev-breezhaler | access-date=29 January 2023}} Doses for inhalation are much lower than oral ones, so that swallowing a dose will not have an effect.{{cite web|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002430/WC500133769.pdf|title=EPAR – Product information for Seebri Breezhaler|publisher=European Medicines Agency|date=28 September 2012|access-date=4 February 2017|archive-date=30 July 2018|archive-url=https://web.archive.org/web/20180730210441/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002430/WC500133769.pdf|url-status=live}}{{cite journal | vauthors = Tzelepis G, Komanapolli S, Tyler D, Vega D, Fulambarker A | title = Comparison of nebulized glycopyrrolate and metaproterenol in chronic obstructive pulmonary disease | journal = The European Respiratory Journal | volume = 9 | issue = 1 | pages = 100–103 | date = January 1996 | pmid = 8834341 | doi = 10.1183/09031936.96.09010100 | doi-access = free }}
Side effects
Dry mouth, urinary retention, headaches, vomiting, diarrhea, constipation, and blurry vision are possible side effects of the medication.
Pharmacology
=Mechanism of action=
Glycopyrronium competitively blocks muscarinic receptors,{{cite journal | vauthors = Chabicovsky M, Winkler S, Soeberdt M, Kilic A, Masur C, Abels C | title = Pharmacology, toxicology and clinical safety of glycopyrrolate | journal = Toxicology and Applied Pharmacology | volume = 370 | pages = 154–169 | date = May 2019 | pmid = 30905688 | doi = 10.1016/j.taap.2019.03.016 | bibcode = 2019ToxAP.370..154C | s2cid = 85498396 }}{{cite journal | vauthors = Haddad EB, Patel H, Keeling JE, Yacoub MH, Barnes PJ, Belvisi MG | title = Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways | journal = British Journal of Pharmacology | volume = 127 | issue = 2 | pages = 413–420 | date = May 1999 | pmid = 10385241 | pmc = 1566042 | doi = 10.1038/sj.bjp.0702573 }} thus inhibiting cholinergic transmission.
=Pharmacokinetics=
Glycopyrronium bromide affects the gastrointestinal tracts, liver and kidney but has a very limited effect on the brain and the central nervous system. In horse studies, after a single intravenous infusion, the observed tendencies of glycopyrronium followed a tri-exponential equation, by rapid disappearance from the blood followed by a prolonged terminal phase. Excretion was mainly in urine and in the form of an unchanged drug. Glycopyrronium has a relatively slow diffusion rate, and in a standard comparison to atropine, is more resistant to penetration through the blood-brain barrier and placenta.{{cite journal | vauthors = Rumpler MJ, Colahan P, Sams RA | title = The pharmacokinetics of glycopyrrolate in Standardbred horses | journal = Journal of Veterinary Pharmacology and Therapeutics | volume = 37 | issue = 3 | pages = 260–268 | date = June 2014 | pmid = 24325462 | doi = 10.1111/jvp.12085 }}
Research
It has been studied in asthma.{{cite journal | vauthors = Hansel TT, Neighbour H, Erin EM, Tan AJ, Tennant RC, Maus JG, Barnes PJ | title = Glycopyrrolate causes prolonged bronchoprotection and bronchodilatation in patients with asthma | journal = Chest | volume = 128 | issue = 4 | pages = 1974–1979 | date = October 2005 | pmid = 16236844 | doi = 10.1378/chest.128.4.1974 | url = http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=16236844 | url-status = dead | archive-url = https://archive.today/20130414111933/http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=16236844 | archive-date = 2013-04-14 }}{{cite journal | vauthors = Gilman MJ, Meyer L, Carter J, Slovis C | title = Comparison of aerosolized glycopyrrolate and metaproterenol in acute asthma | journal = Chest | volume = 98 | issue = 5 | pages = 1095–1098 | date = November 1990 | pmid = 2225951 | doi = 10.1378/chest.98.5.1095 | url = http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=2225951 | url-status = dead | archive-url = https://archive.today/20130414121303/http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=2225951 | archive-date = 2013-04-14 }}
References
{{reflist}}
{{Drugs for functional gastrointestinal disorders}}
{{Drugs for obstructive airway diseases}}
{{Muscarinic acetylcholine receptor modulators}}
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