Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Pentoxyverine: Difference between pages

{{Short description|Antitussive / cough suppressant}}

| verifiedrevid = 461940880

| tradename =

| legal_US =

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| bioavailability =

| protein_bound =

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 77-23-6

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| C=20 | H=31 | N=1 | O=3

| melting_point = 90

| melting_high = 95

| solubility = good

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'''Pentoxyverine''' ([[International Nonproprietary Name|rINN]]) or '''carbetapentane''' is an [[antitussive]] (cough suppressant) commonly used for cough associated with illnesses like [[common cold]]. It is sold [[over-the-counter drug|over-the-counter]] as '''Solotuss''',<ref name="Drugs.com">{{cite web

| publisher = Drugs.com

| url = https://www.drugs.com/mtm/carbetapentane.html

| title = Carbetapentane

| access-date = 2018-01-23

| archive-date = 2008-07-26

| archive-url = https://web.archive.org/web/20080726050149/https://www.drugs.com/mtm/carbetapentane.html

| url-status = dead

}}</ref> or in combination with other medications, especially [[decongestant]]s. One such product is ''Certuss'', a combination of [[guaifenesin]] and pentoxyverine.<ref>

{{cite web

| publisher = Drugs.com

| url = https://www.drugs.com/mtm/certuss.html

| title = Certuss

}}</ref> The drug has been available in the form of drops, [[suspension (chemistry)|suspension]]s and [[suppositories]].<ref name="Drugs.com" /><ref name="AustriaCodex">{{cite book | title = Austria-Codex | veditors = Jasek W | publisher = Österreichischer Apothekerverlag | location = Vienna | year = 2008 | edition = 63 | isbn = 978-3-85200-188-3 | language = German }}</ref>

It was formerly available over-the-counter in United States. However, the [[U.S. Food & Drug Administration]] ruled in 1987 that pentoxyverine was not generally recognized as safe and effective and ordered it to be removed from the over-the-counter market.<ref>{{Cite web | vauthors = Shuren J |date=November 30, 2007 |title=Technical Amendment: Removes carbetapentane citrate from 21 CFR 310.201(a)(20) |url=https://www.govinfo.gov/content/pkg/FR-2007-11-30/pdf/E7-23207.pdf |archive-url=https://web.archive.org/web/20210406154702/https://www.govinfo.gov/content/pkg/FR-2007-11-30/pdf/E7-23207.pdf |archive-date=April 6, 2021 |access-date=November 3, 2023 |website=Govinfo |publisher=[[Food and Drug Administration]]}}</ref>

==Uses==

The drug is used for the treatment of dry cough associated with conditions such as common cold, [[bronchitis]] or [[sinusitis]]. Like [[codeine]] and other antitussives, it relieves the symptom, but does not heal the illness.<ref name="Drugs.com" /> No controlled [[clinical trial]]s regarding the efficiency of pentoxyverine are available.<ref name="Arzneistoff-Profile" /> In

[[Pharmacologist]]s use the substance as a selective [[agonist]] at the [[sigma-1 receptor]] in animal<ref name="Brown">

{{cite journal | vauthors = Brown C, Fezoui M, Selig WM, Schwartz CE, Ellis JL | title = Antitussive activity of sigma-1 receptor agonists in the guinea-pig | journal = British Journal of Pharmacology | volume = 141 | issue = 2 | pages = 233–40 | date = January 2004 | pmid = 14691051 | pmc = 1574192 | doi = 10.1038/sj.bjp.0705605 }}</ref> and [[in vitro]] experiments.<ref>

{{cite journal | vauthors = Kume T, Nishikawa H, Taguchi R, Hashino A, Katsuki H, Kaneko S, Minami M, Satoh M, Akaike A | display-authors = 6 | title = Antagonism of NMDA receptors by sigma receptor ligands attenuates chemical ischemia-induced neuronal death in vitro | journal = European Journal of Pharmacology | volume = 455 | issue = 2–3 | pages = 91–100 | date = November 2002 | pmid = 12445574 | doi = 10.1016/S0014-2999(02)02582-7 }}</ref><ref>{{cite web | url = http://www.chemicalbook.cn/ProductChemicalPropertiesCB2476609_EN.htm | title = Carbetapentane Citrate CAS#: 23142-01-0 | work = Chemical Book }}</ref>

==Contraindications==

Pentoxyverine is contraindicated in persons with [[bronchial asthma]]<ref name="Arzneistoff-Profile">

{{cite book | title = Arzneistoff-Profile | veditors = Dinnendahl V, Fricke U | publisher = Govi Pharmazeutischer Verlag | location = Eschborn, Germany | date = 2010 | edition = 23rd | volume = 4 | isbn = 978-3-7741-9846-3 | language = German }}</ref> or other kinds of [[respiratory insufficiency]] (breathing difficulties), as well as angle-closure [[glaucoma]]. No data are available for the use of pentoxyverine during pregnancy, [[lactation]], or children under two years of age, wherefore the drug must not be used under these circumstances.<ref name="AustriaCodex" />

Antitussive drugs are not useful in patients with extensive [[phlegm]] production because they prevent coughing up the phlegm.<ref name="Arzneistoff-Profile" />

==Adverse effects==

The most common side effects (seen in more than 1% of patients) are upper abdominal (belly) pain, diarrhoea, dry mouth, and nausea or vomiting. [[Allergic reaction]]s of the skin like itching, rashes, [[hives]] and [[angiooedema]] are rare. The same is true for [[anaphylactic shock]] and [[convulsion]]s.<ref name="AustriaCodex" /><ref>

{{cite book | title = Rote Liste | veditors = Dootz H, Kuhlmann A, Hoffmann K | at = 24&nbsp;037 | edition = 2005 | isbn = 978-3-87193-306-6 | publisher = Editio Cantor | location = Aulendorf | language = German | year = 2005 }}</ref>

==Overdose==

Overdosage leads to drowsiness, [[Psychomotor agitation|agitation]], nausea and [[anticholinergic]] effects like [[tachycardia]] (high heart rate), dry mouth, blurred vision, glaucoma, or [[urinary retention]].<ref name="Drugs.com" /><ref name="AustriaCodex" /> Especially in children, pentoxyverine can cause [[hypoventilation]],<ref name="Arzneistoff-Profile" /> but much more seldom than codeine and other [[opioid]] antitussives.

The treatment of overdosage aims at the symptoms; there are no specific [[antidote]]s available.<ref name="AustriaCodex" />

== Interactions ==

No interactions have been described at usual doses. It is possible that pentoxyverine can increase the potency of sedative drugs like [[benzodiazepine]]s, some [[anticonvulsant]]s and [[antidepressant]]s, and alcohol. Likewise, some consumer informations warn patients from taking the drug in combination with or up to two weeks after [[monoamine oxidase inhibitor]]s, which are known to cause potentially fatal reactions in combination with the (chemically only distantly related) antitussive [[dextromethorphan]].<ref name="Drugs.com" /><ref name="AustriaCodex" /><ref name="Arzneistoff-Profile" />

==Mechanism of action==

Pentoxyverine is believed to suppress the [[cough reflex]] in the [[central nervous system]],<ref name="Drugs.com" /> but the exact mechanism of action is not known with certainty. The drug acts as an [[Receptor antagonist|antagonist]] at [[muscarinic receptors]]<ref name="AustriaCodex" /> (subtype [[M1 receptor|M₁]]) and as an agonist at [[sigma receptor]]s (subtype σ₁)<ref name="Brown" /> with an [[IC50|IC₅₀]] of 9 nM.<ref>{{cite journal | vauthors = Klein M, Musacchio JM | title = Dextromethorphan binding sites in the guinea pig brain. | journal = Cellular and Molecular Neurobiology | volume = 8 | issue = 2 | pages = 149–156 | date = October 10, 1988 | doi = 10.1007/BF00711241 | pmid = 3044591 | s2cid = 33844132 }}</ref> Its [[anticholinergic]] properties can theoretically relax the [[pulmonary alveoli]] and reduce phlegm production. [[Antispasmodic|Spasmolytic]] and local anaesthetic properties have also been described.<ref name="Arzneistoff-Profile" /> The clinical relevance of these mechanisms is uncertain.

==Pharmacokinetics==

The substance is absorbed quickly from the gut and reaches its [[Cmax (pharmacology)|maximum plasma concentration]] (C_max) after about two hours. If applied rectally, C_max is reached after four hours. The [[bioavailability]] of the suppositories, measured as [[Area under the curve (pharmacokinetics)|area under the curve]] (AUC), is about twofold that of oral formulations, due to a [[first pass effect]] of over 50%. By far the most important metabolisation reaction is [[ester hydrolysis]], which accounts for 26.3% of the total clearance through the kidneys. Only 0.37% are cleared in form of the original substance.<ref name="AustriaCodex" /> The [[Biological half-life|plasma half life]] is 2.3 hours for oral formulations and three to 3.5 hours for suppositories.<ref>

{{cite book | vauthors = Steinhilber D, Schubert-Zsilavecz M, Roth HJ | title = Medizinische Chemie |trans-title=Medical Chemistry

| year = 2005 | publisher = Deutscher Apothekerverlag | location = Stuttgart | language = German | isbn = 978-3-7692-3483-1 | page = 190 }}</ref> Pentoxyverine is also excreted into the [[breast milk]].<ref name="AustriaCodex" />

==Chemical properties==

Pentoxyverine dihydrogen [[citrate]], the salt that is commonly used for oral preparations, is a white to off-white, crystalline powder. It dissolves easily in water or [[chloroform]], but not in [[benzene]], [[diethyl ether]], or [[petroleum ether]]. It melts at {{convert|90 to 95|C|F}}.<ref name="Arzneistoff-Profile" /> Other orally available salts are the [[hydrochloride]] and the [[tannate]];<ref>{{cite web | website = [[Monthly Index of Medical Specialities|MIMS]] | url = http://www.mims.com/USA/drug/info/pentoxyverine?type=full&h=pentoxyverine | title = Pentoxyverine Full Prescribing Information }}</ref> suppositories contain the free base.<ref name="AustriaCodex" />

== See also ==

* [[Cough syrup]]

* [[Noscapine]]

* [[Codeine]]; [[Pholcodine]]

* [[Dextromethorphan]]; [[Dimemorfan]]

* [[Racemorphan]]; [[Dextrorphan]]; [[Levorphanol]]

* [[Butamirate]]

* [[Tipepidine]]

* [[Cloperastine]]; [[Levocloperastine]]

== References ==

{{Reflist|32em}}

{{Cough and cold preparations}}

{{Sigma receptor modulators}}

[[Category:Antitussives]]

[[Category:Carboxylate esters]]

[[Category:Ethers]]

[[Category:Diethylamino compounds]]

[[Category:Sigma agonists]]

[[Category:Cyclopentanes]]