Pentoxyverine
Encyclopedia
Pentoxyverine or carbetapentane is an antitussive (cough suppressant) commonly used for cough associated with illnesses like common cold
. It is sold over-the-counter
in the United States as Solotuss, or in combination with other medications, especially decongestant
s. One such product is Certuss, a combination of guaifenesin
and pentoxyverine.
The drug is available in the form of drops, suspension
s and suppositories.
or sinusitis
. Like codeine
and other antitussives, it relieves the symptom, but does not heal the illness. No controlled clinical trial
s regarding the efficiency of pentoyxverine are available.
Pharmacologists use the substance as a selective agonist
at the sigma-1 receptor
in animal and in vitro
experiments.
. 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.
Antitussive drugs are not useful in patients with extensive phlegm
production because they prevent coughing up the phlem.
s.
, nausea and anticholinergic
effects like tachycardia
(high heart rate), dry mouth, blurred vision, glaucoma, or urinary retention
. Especially in children, pentoxyverine can cause hypoventilation
, 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.
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
.
in the central nervous system
, but the exact mechanism of action is not known with certainty. The drug acts as an antagonist
at muscarinic receptors (subtype M1) and as an agonist at sigma receptor
s (subtype σ1). Its anticholinergic
properties can theoretically relax the pulmonary alveoli and reduce phlegm production. Spasmolytic
and local anaesthetic properties have also been described. The clinical relevance of these mechanisms is uncertain.
of the suppositories, measured as 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. 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
.
, 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
, and melts at 90–95 °C. Other orally available salts are the hydrochloride
and the tannate
; suppositories contain the free base.
Common cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
. It is sold over-the-counter
Over-the-counter drug
Over-the-counter drugs are medicines that may be sold directly to a consumer without a prescription from a healthcare professional, as compared to prescription drugs, which may be sold only to consumers possessing a valid prescription...
in the United States as Solotuss, or in combination with other medications, especially decongestant
Decongestant
A decongestant or nasal decongestant is a type of drug that is used to relieve nasal congestion.-Pharmacology:The vast majority of decongestants act via enhancing norepinephrine and epinephrine or adrenergic activity by stimulating the α-adrenergic receptors...
s. One such product is Certuss, a combination of guaifenesin
Guaifenesin
Guaifenesin INN or guaiphenesin , also glyceryl guaiacolate, is an expectorant drug sold over the counter and usually taken by mouth to assist the bringing up of phlegm from the airways in acute respiratory tract infections.-History:Similar medicines derived from the guaiac tree were in use as a...
and pentoxyverine.
The drug is available in the form of drops, suspension
Suspension (chemistry)
In chemistry, a suspension is a heterogeneous fluid containing solid particles that are sufficiently large for sedimentation. Usually they must be larger than 1 micrometer. The internal phase is dispersed throughout the external phase through mechanical agitation, with the use of certain...
s and suppositories.
Uses
The drug is used for the treatment of dry cough associated with conditions such as common cold, bronchitisBronchitis
Acute bronchitis is an inflammation of the large bronchi in the lungs that is usually caused by viruses or bacteria and may last several days or weeks. Characteristic symptoms include cough, sputum production, and shortness of breath and wheezing related to the obstruction of the inflamed airways...
or sinusitis
Sinusitis
Sinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days...
. Like codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
and other antitussives, it relieves the symptom, but does not heal the illness. No controlled clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s regarding the efficiency of pentoyxverine are available.
Pharmacologists use the substance as a selective agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
at the sigma-1 receptor
Sigma-1 receptor
The sigma-1 receptor is a chaperone protein at the endoplasmatic reticulum that modulates calcium signaling through the IP3 receptor. In humans, the sigma-1 receptor is encoded by the SIGMAR1 gene....
in animal and in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
experiments.
Contraindications
Pentoxyverine is contraindicated in persons with bronchial asthma or other kinds of respiratory insufficiency (breathing difficulties), as well as angle-closure glaucomaGlaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
. No data are available for the use of pentoxyverine during pregnancy, lactation
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 occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
, 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
Phlegm is a liquid secreted by the mucous membranes of mammalians. Its definition is limited to the mucus produced by the respiratory system, excluding that from the nasal passages, and particularly that which is expelled by coughing . Phlegm is in essence a water-based gel consisting of...
production because they prevent coughing up the phlem.
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 reactions of the skin like itching, rashes, hives and angiooedema are rare. The same is true for anaphylactic shock and convulsionConvulsion
A convulsion is a medical condition where body muscles contract and relax rapidly and repeatedly, resulting in an uncontrolled shaking of the body. Because a convulsion is often a symptom of an epileptic seizure, the term convulsion is sometimes used as a synonym for seizure...
s.
Overdose
Overdosage leads to drowsiness, agitationAgitation
Agitation may refer to:* Agitation , putting into motion by shaking or stirring* Emotional state of excitement or restlessness** Psychomotor agitation, an extreme form of the above, which can be a side effect of antipsychotic medication...
, nausea and anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
effects like tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
(high heart rate), dry mouth, blurred vision, glaucoma, or urinary retention
Urinary retention
Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
. Especially in children, pentoxyverine can cause hypoventilation
Hypoventilation
In medicine, hypoventilation occurs when ventilation is inadequate to perform needed gas exchange...
, but much more seldom than codeine and other opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
antitussives.
The treatment of overdosage aims at the symptoms; there are no specific antidote
Antidote
An antidote is a substance which can counteract a form of poisoning. The term ultimately derives from the Greek αντιδιδοναι antididonai, "given against"....
s available.
Interactions
No interactions have been described at usual doses. It is possible that pentoxyverine can increase the potency of sedative drugs like benzodiazepineBenzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s, some anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
s and antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
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 inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
s, which are known to cause potentially fatal reactions in combination with the (chemically only distantly related) antitussive dextromethorphan
Dextromethorphan
Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...
.
Mechanism of action
Pentoxyverine suppresses the cough reflexCough reflex
The cough reflex has both sensory and motor components. Pulmonary irritant receptors in the epithelium of the respiratory tract are sensitive to both mechanical and chemical stimuli...
in the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, but the exact mechanism of action is not known with certainty. The drug acts as an antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
at muscarinic receptors (subtype M1) and as an agonist at sigma receptor
Sigma receptor
The sigma receptors σ1 and σ2 bind to ligands such as 4-PPBP, SA 4503, ditolylguanidine, dimethyltryptamine and siramesine.- Classification :...
s (subtype σ1). Its anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
properties can theoretically relax the pulmonary alveoli and reduce phlegm production. Spasmolytic
Spasmolytic
Spasmolytic may refer to:* A type of muscle relaxant* "Spasmolytic" , by Canadian band Skinny Puppy...
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 (Cmax) after about two hours. If applied rectally, Cmax is reached after four hours. The bioavailabilityBioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
of the suppositories, measured as area under the curve (AUC), is about twofold that of oral formulations, due to a first pass effect
First pass effect
The first-pass effect is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall...
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. The plasma half life
Biological half-life
The biological half-life or elimination half-life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...
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
Breast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...
.
Chemical properties
Pentoxyverine dihydrogen citrateCitrate
A citrate can refer either to the conjugate base of citric acid, , or to the esters of citric acid. An example of the former, a salt is trisodium citrate; an ester is triethyl citrate.-Other citric acid ions:...
, 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
Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...
, but not in benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
, diethyl ether
Diethyl ether
Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
, or petroleum ether
Petroleum ether
Petroleum ether, also known as benzine, VM&P Naphtha, Petroleum Naphtha, Naphtha ASTM, Petroleum Spirits, X4 or Ligroin, is a group of various volatile, highly flammable, liquid hydrocarbon mixtures used chiefly as nonpolar solvents...
, and melts at 90–95 °C. Other orally available salts are the hydrochloride
Hydrochloride
In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base . This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid....
and the tannate
Tannate
A tannate is the salt or ester of tannic acid. Albumin tannate is an antidiarrheal....
; suppositories contain the free base.