Pentoxyverine (

rINN Rinn is a municipality in the district of Innsbruck-Land in the Austrian state of Tyrol located 6 km southeast of Innsbruck. The village was mentioned in documents as “Runne” in 1250 for the first time. Population Climate Climate typ ...

) or carbetapentane is an

antitussive Cold medicines are a group of medications taken individually or in combination as a treatment for the symptoms of the common cold and similar conditions of the upper respiratory tract. The term encompasses a broad array of drugs, including a ...

(cough suppressant) commonly used for cough associated with illnesses like

common cold The common cold or the cold is a viral infectious disease of the upper respiratory tract that primarily affects the respiratory mucosa of the nose, throat, sinuses, and larynx. Signs and symptoms may appear fewer than two days after exposu ...

. It is sold

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid prescr ...

in the United States as Solotuss, or in combination with other medications, especially

decongestant A decongestant, or nasal decongestant, is a type of pharmaceutical drug that is used to relieve nasal congestion in the upper respiratory tract. The active ingredient in most decongestants is either pseudoephedrine or phenylephrine (the latter of ...

s. One such product is ''Certuss'', a combination of

guaifenesin Guaifenesin, also known as glyceryl guaiacolate, is an expectorant medication that aids in the elimination of sputum from the respiratory tract. Chemically it is an ether of guaiacol and glycerine. It is often used in combination with other me ...

and pentoxyverine. The drug is available in the form of drops,

suspension Suspension or suspended may refer to: Science and engineering * Suspension (topology), in mathematics * Suspension (dynamical systems), in mathematics * Suspension of a ring, in mathematics * Suspension (chemistry), small solid particles suspend ...

s and

suppositories A suppository is a dosage form used to deliver medications by insertion into a body orifice where it dissolves or melts to exert local or systemic effects. There are three types of suppositories, each to insert into a different sections: rectal su ...

Uses

The drug is used for the treatment of dry cough associated with conditions such as common cold,

bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. ...

sinusitis Sinusitis, also known as rhinosinusitis, is inflammation of the nasal mucosa, mucous membranes that line the paranasal sinuses, sinuses resulting in symptoms that may include thick Mucus#Respiratory system, nasal mucus, a nasal congestion, plugg ...

. Like

codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

and other antitussives, it relieves the symptom, but does not heal the illness. No controlled

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s regarding the efficiency of pentoxyverine are available.

Pharmacologist Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

s use the substance as a selective

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

at the

sigma-1 receptor The sigma-1 receptor (σ1R), one of two sigma receptor subtypes, is a chaperone protein at the endoplasmic reticulum (ER) that modulates calcium signaling through the IP3 receptor. In humans, the σ1 receptor is encoded by the ''SIGMAR1'' gene. ...

in animal and

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

experiments.

Contraindications

Pentoxyverine is contraindicated in persons with

bronchial asthma Asthma is a long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wheezing, coug ...

or other kinds of

respiratory insufficiency Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise ...

(breathing difficulties), as well as angle-closure

glaucoma Glaucoma is a group of eye diseases that result in damage to the optic nerve (or retina) and cause vision loss. The most common type is open-angle (wide angle, chronic simple) glaucoma, in which the drainage angle for fluid within the eye rem ...

. No data are available for the use of pentoxyverine during pregnancy,

lactation Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process naturally occurs with all sexually mature female mammals, although it may predate mammals. The proces ...

, or children under two years of age, wherefore the drug must not be used under these circumstances. Antitussive drugs are not useful in patients with extensive

phlegm Phlegm (; , ''phlégma'', "inflammation", "humour caused by heat") is mucus produced by the respiratory system, excluding that produced by the nasal passages. It often refers to respiratory mucus expelled by coughing, otherwise known as sputum ...

production because they prevent coughing up the phlegm.

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 Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

s of the skin like itching, rashes,

hives Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

and

angiooedema Angioedema is an area of swelling ( edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which a ...

are rare. The same is true for

anaphylactic shock Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follow ...

and

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...

Overdose

Overdosage leads to drowsiness, agitation, nausea and

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system ...

effects like

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

(high heart rate), dry mouth, blurred vision, glaucoma, or

urinary retention Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladd ...

. Especially in children, pentoxyverine can cause

hypoventilation Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (''hypo'' meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia ...

, but much more seldom than codeine and other

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

antitussives. The treatment of overdosage aims at the symptoms; there are no specific

antidote An antidote is a substance that can counteract a form of poisoning. The term ultimately derives from the Greek term φάρμακον ἀντίδοτον ''(pharmakon) antidoton'', "(medicine) given as a remedy". Antidotes for anticoagulants are s ...

s available.

Interactions

No interactions have been described at usual doses. It is possible that pentoxyverine can increase the potency of sedative drugs like

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

s, some

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...

s and

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

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 Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espe ...

s, which are known to cause potentially fatal reactions in combination with the (chemically only distantly related) antitussive

dextromethorphan Dextromethorphan (DXM) is a medication most often used as a cough suppressant in over-the-counter cold and cough medicines. It is sold in syrup, tablet, spray, and lozenge forms. In 2022, the FDA approved a formulation of it combined with bu ...

Mechanism of action

Pentoxyverine suppresses the

cough reflex The cough reflex occurs when stimulation of cough receptors in the respiratory tract by dust or other foreign particles produces a cough, which causes rapidly moving air which usually remove the foreign material before it reaches the lungs. This ty ...

in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

, but the exact mechanism of action is not known with certainty. The drug acts as an antagonist at

muscarinic receptors Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...

(subtype M₁) and as an agonist at

sigma receptor Sigma receptors (σ-receptors) are protein cell surface receptors that bind ligands such as 4-PPBP (4-phenyl-1-(4-phenylbutyl) piperidine), SA 4503 (cutamesine), ditolylguanidine, dimethyltryptamine, and siramesine. There are two subtypes, ...

s (subtype σ₁) with an IC₅₀ of 9 nM. Its

properties can theoretically relax the

pulmonary alveoli A pulmonary alveolus (plural: alveoli, from Latin ''alveolus'', "little cavity"), also known as an air sac or air space, is one of millions of hollow, distensible cup-shaped cavities in the lungs where oxygen is exchanged for carbon dioxide. A ...

and reduce phlegm production. Spasmolytic and local anaesthetic properties have also been described. The clinical relevance of these mechanisms is uncertain.

Pharmacokinetics

The substance is absorbed quickly from the gut and reaches its maximum plasma concentration (C_max) after about two hours. If applied rectally, C_max is reached after four hours. The

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

of the suppositories, measured as

area under the curve In mathematics, an integral assigns numbers to functions in a way that describes displacement, area, volume, and other concepts that arise by combining infinitesimal data. The process of finding integrals is called integration. Along with ...

(AUC), is about twofold that of oral formulations, due to a

first pass effect The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemi ...

of over 50%. By far the most important metabolisation reaction is

ester hydrolysis In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are fa ...

, which accounts for 26.3% of the total clearance through the kidneys. Only 0.37% are cleared in form of the original substance. The plasma half life is 2.3 hours for oral formulations and three to 3.5 hours for suppositories. Pentoxyverine is also excreted into the

breast milk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates ( lacto ...

Chemical properties

Pentoxyverine dihydrogen

citrate Citric acid is an organic compound with the chemical formula HOC(CO2H)(CH2CO2H)2. It is a colorless weak organic acid. It occurs naturally in citrus fruits. In biochemistry, it is an intermediate in the citric acid cycle, which occurs in t ...

, the salt that is commonly used for oral preparations, is a white to off-white, crystalline powder. It dissolves easily in water or

chloroform Chloroform, or trichloromethane, is an organic compound with chemical formula, formula Carbon, CHydrogen, HChlorine, Cl3 and a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to ...

, but not in

benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms, ...

diethyl ether Diethyl ether, or simply ether, is an organic compound in the ether class with the formula , sometimes abbreviated as (see Pseudoelement symbols). It is a colourless, highly volatile, sweet-smelling ("ethereal odour"), extremely flammable liq ...

, or

petroleum ether Petroleum ether is the petroleum fraction consisting of aliphatic hydrocarbons and boiling in the range 35–60 °C, and commonly used as a laboratory solvent. Despite the name, petroleum ether is not classified as an ether; the term is used ...

. It melts at . Other orally available salts are the

hydrochloride In chemistry, a hydrochloride is an acid salt resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (e.g. an amine). An alternative name is chlorhydrate, which comes from French. An archaic alternative na ...

and the tannate; suppositories contain the free base.

References

{{Sigma receptor modulators Antitussives Carboxylate esters Ethers Diethylamino compounds Sigma agonists Cyclopentanes