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| Clinical data | |
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| AHFS/Drugs.com | International Drug Names |
| MedlinePlus | a606008 |
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| Routes of administration | Oral, rectal |
| ATC code | |
| Pharmacokinetic data | |
| Metabolism | Hepatic |
| Eliminationhalf-life | 2.3 hours (oral), 3–3.5 hours (rectal) |
| Excretion | Renal |
| Identifiers | |
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| CAS Number |
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| PubChemCID | |
| ChemSpider |
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| UNII | |
| KEGG |
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| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.000.923 |
| Chemical and physical data | |
| Formula | C20H31NO3 |
| Molar mass | 333.472 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 90 to 95 °C (194 to 203 °F) |
| Solubility in water | good |
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Pentoxyverine (rINN) orcarbetapentane is anantitussive (cough suppressant) commonly used for cough associated with illnesses likecommon cold. It is soldover-the-counter asSolotuss,[1] or in combination with other medications, especiallydecongestants. One such product isCertuss, a combination ofguaifenesin and pentoxyverine.[2] The drug has been available in the form of drops,suspensions andsuppositories.[1][3]
It was formerly available over-the-counter in United States. However, theU.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.[4]
The drug is used for the treatment of dry cough associated with conditions such as common cold,bronchitis orsinusitis. Likecodeine and other antitussives, it relieves the symptom, but does not heal the illness.[1] No controlledclinical trials regarding the efficiency of pentoxyverine are available.[5]
Pharmacologists use the substance as a selectiveagonist at thesigma-1 receptor in animal[6] andin vitro experiments.[7][8]
Pentoxyverine is contraindicated in persons withbronchial asthma[5] or other kinds ofrespiratory insufficiency (breathing difficulties), as well as angle-closureglaucoma. 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.[3]
Antitussive drugs are not useful in patients with extensivephlegm production because they prevent coughing up the phlegm.[5]
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 reactions of the skin like itching, rashes,hives andangiooedema are rare. The same is true foranaphylactic shock andconvulsions.[3][9]
Overdosage leads to drowsiness,agitation, nausea andanticholinergic effects liketachycardia (high heart rate), dry mouth, blurred vision, glaucoma, orurinary retention.[1][3] Especially in children, pentoxyverine can causehypoventilation,[5] but much more seldom than codeine and otheropioid antitussives.
The treatment of overdosage aims at the symptoms; there are no specificantidotes available.[3]
No interactions have been described at usual doses. It is possible that pentoxyverine can increase the potency of sedative drugs likebenzodiazepines, someanticonvulsants andantidepressants, and alcohol. Likewise, some consumer informations warn patients from taking the drug in combination with or up to two weeks aftermonoamine oxidase inhibitors, which are known to cause potentially fatal reactions in combination with the (chemically only distantly related) antitussivedextromethorphan.[1][3][5]
Pentoxyverine is believed to suppress thecough reflex in thecentral nervous system,[1] but the exact mechanism of action is not known with certainty. The drug acts as anantagonist atmuscarinic receptors[3] (subtypeM1) and as an agonist atsigma receptors (subtype σ1)[6] with anIC50 of 9 nM.[10] Itsanticholinergic properties can theoretically relax thepulmonary alveoli and reduce phlegm production.Spasmolytic and local anaesthetic properties have also been described.[5] The clinical relevance of these mechanisms is uncertain.
The substance is absorbed quickly from the gut and reaches itsmaximum plasma concentration (Cmax) after about two hours. If applied rectally, Cmax is reached after four hours. Thebioavailability of the suppositories, measured asarea under the curve (AUC), is about twofold that of oral formulations, due to afirst pass effect of over 50%. By far the most important metabolisation reaction isester hydrolysis, which accounts for 26.3% of the total clearance through the kidneys. Only 0.37% are cleared in form of the original substance.[3] Theplasma half life is 2.3 hours for oral formulations and three to 3.5 hours for suppositories.[11] Pentoxyverine is also excreted into thebreast milk.[3]
Pentoxyverine dihydrogencitrate, the salt that is commonly used for oral preparations, is a white to off-white, crystalline powder. It dissolves easily in water orchloroform, but not inbenzene,diethyl ether, orpetroleum ether. It melts at 90 to 95 °C (194 to 203 °F).[5] Other orally available salts are thehydrochloride and thetannate;[12] suppositories contain the free base.[3]