Noscapine
Encyclopedia
Noscapine is a benzylisoquinoline
alkaloid
from plants of the Papaveraceae
family, without significant painkilling
properties. This agent is primarily used for its antitussive (cough-suppressing) effects. It has also been shown to have anticancer activity.
, and also isolated in 1832 another very important component of raw opium, that he called codeine
, today's probably most widely used opium-originating component).
ring is unstable and opens in basic media. The opposite reaction is presented in acidic media.
The bond C1-C3' is also unstable. This is the bond connecting the two optically active carbon atoms. In aqueous solution of sulfuric acid
and heating it dissociates into cotarnine (4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline) and opic acid (6-formyl-2,3-dimethoxybenzoic acid). When noscapine is reduced with zinc
/HCl
, the bond C1-C3' saturates and the molecule dissociates into hydrocotarnine (2-hydroxycotarnine) and meconine (6,7-dimethoxyisobenzofuran-1(3H)-one).
, a sigma specific antagonist
, causes a dose-dependent reduction in antitussive activity of noscapine.
s and hypoxic ischemia
in stroke
patients. In cancer treatment, noscapine appears to interfere with microtubule
function, and thus the division of cancer cells in a way similar to the taxanes. Early studies in treatment of prostate cancer
are very promising.
In stroke patients, noscapine blocks the bradykinin
e b-2 receptors. A 2003 study in Iran showed a dramatic decrease in mortality in patients treated with noscapine.
Studies are currently underway to assess the effectiveness of this drug in cancer and stroke treatment. Noscapine is non-addictive, widely available, has a low side-effect
incidence, and is easily administered orally, thus it has great potential for use, especially in developing countries.
abuse in several countries, being readily available from local pharmacies without a prescription.
The effects, beginning around 45 to 120 mins after consumption, are similar to dextromethorphan
and alcohol intoxication. Unlike dextromethorphan, noscapine is not an NMDA receptor antagonist
.
, the average noscapine concentration was around 8%.
Noscapine has also been used to identify drug users who are taking street heroin at the same time as prescribed diamorphine. Since the diamorphine in street heroin is the same as the pharmaceutical diamorphine, examination of the contaminants is the only way to test whether street heroin has been used. Other contaminants used in urine
samples alongside noscapine include papaverine
and acetylcodeine. Noscapine is metabolised by the body, and is itself rarely found in urine, instead being present as the primary metabolites, cotarnine and meconine. Detection is performed by gas chromatography-mass spectrometry
or liquid chromatography-mass spectrometry (LCMS) but can also use a variety of other analytical techniques.
The effects shown above are not permanent.
Noscapine should not be taken with any MAOIs (monoamine oxidase inhibitors), as unknown and potentially fatal effects may occur.
Noscapine should not be taken in conjunction with warfarin. The anticoagulant effects of warfarin are drastically increased by noscapine, leading to serious and possibly fatal thinning of the blood.
Benzylisoquinoline
1-Benzylisoquinoline is a chemical compound, and the structural backbone of many alkaloids with a wide variety of structures, including papaverine, noscapine, codeine, morphine, apomorphine, berberine, protopine and tubocurarine.-Biosynthesis:...
alkaloid
Alkaloid
Alkaloids are a group of naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids...
from plants of the Papaveraceae
Papaveraceae
Papaveraceae, informally known as the poppy family, are an economically important family of 44 genera and approximately 770 species of flowering plants in the order Ranunculales. The family is cosmopolitan, occurring in temperate and subtropical climates, but almost unknown in the tropics...
family, without significant painkilling
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
properties. This agent is primarily used for its antitussive (cough-suppressing) effects. It has also been shown to have anticancer activity.
History
Noscapine was first isolated and characterized in chemical breakdown and properties in 1817 under the denomination of "Narcotine" by Pierre Robiquet, a French chemist in Paris (Robiquet conducted over 20 years between 1815 and 1835 a series of studies in the enhancement of methods for the isolation of morphineMorphine
Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...
, and also isolated in 1832 another very important component of raw opium, that he called codeine
Codeine
Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...
, today's probably most widely used opium-originating component).
Structure analysis
The lactoneLactone
In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
ring is unstable and opens in basic media. The opposite reaction is presented in acidic media.
The bond C1-C3' is also unstable. This is the bond connecting the two optically active carbon atoms. In aqueous solution of sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
and heating it dissociates into cotarnine (4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]isoquinoline) and opic acid (6-formyl-2,3-dimethoxybenzoic acid). When noscapine is reduced with zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
/HCl
HCL
HCL or HCl can stand for:* Hairy cell leukemia, an uncommon and slowly progressing B cell leukemia* Hardware compatibility list...
, the bond C1-C3' saturates and the molecule dissociates into hydrocotarnine (2-hydroxycotarnine) and meconine (6,7-dimethoxyisobenzofuran-1(3H)-one).
Mechanism of action
Noscapine's antitussive effects appear to be primarily mediated by its sigma receptor agonist activity. Evidence for this mechanism is suggested by experimental evidence in rats. Pretreatment with rimcazoleRimcazole
Rimcazole is an antagonist of the sigma receptor as well as a dopamine reuptake inhibitor. Sigma receptors are thought to be involved in the drug psychosis that can be induced by some drugs such as PCP and cocaine, and rimcazole was originally researched as a potential antipsychotic with a...
, a sigma specific 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...
, causes a dose-dependent reduction in antitussive activity of noscapine.
Cancer and stroke treatment
Noscapine is currently under investigation for use in the treatment of several cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s and hypoxic ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
in stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
patients. In cancer treatment, noscapine appears to interfere with microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
function, and thus the division of cancer cells in a way similar to the taxanes. Early studies in treatment of prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
are very promising.
In stroke patients, noscapine blocks the bradykinin
Bradykinin
Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...
e b-2 receptors. A 2003 study in Iran showed a dramatic decrease in mortality in patients treated with noscapine.
Studies are currently underway to assess the effectiveness of this drug in cancer and stroke treatment. Noscapine is non-addictive, widely available, has a low side-effect
Adverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
incidence, and is easily administered orally, thus it has great potential for use, especially in developing countries.
Abuse
Noscapine has a history of over-the-counter drugOver-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...
abuse in several countries, being readily available from local pharmacies without a prescription.
The effects, beginning around 45 to 120 mins after consumption, are similar to 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...
and alcohol intoxication. Unlike dextromethorphan, noscapine is not an NMDA receptor antagonist
NMDA receptor antagonist
NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the N-methyl d-aspartate receptor . They are used as anesthesia for animals and, less commonly, for humans; the state of anesthesia they induce is referred to as dissociative anesthesia...
.
Noscapine in heroin
Noscapine can survive the manufacturing processes of heroin and can be found in street heroin. This is useful for law enforcement agencies, as the amounts of contaminants can identify the source of seized drugs. In 2005 in Liège, BelgiumBelgium
Belgium , officially the Kingdom of Belgium, is a federal state in Western Europe. It is a founding member of the European Union and hosts the EU's headquarters, and those of several other major international organisations such as NATO.Belgium is also a member of, or affiliated to, many...
, the average noscapine concentration was around 8%.
Noscapine has also been used to identify drug users who are taking street heroin at the same time as prescribed diamorphine. Since the diamorphine in street heroin is the same as the pharmaceutical diamorphine, examination of the contaminants is the only way to test whether street heroin has been used. Other contaminants used in urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
samples alongside noscapine include papaverine
Papaverine
Papaverine is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasm, vasospasm , and occasionally in the treatment of erectile dysfunction...
and acetylcodeine. Noscapine is metabolised by the body, and is itself rarely found in urine, instead being present as the primary metabolites, cotarnine and meconine. Detection is performed by gas chromatography-mass spectrometry
Gas chromatography-mass spectrometry
Gas chromatography–mass spectrometry is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample. Applications of GC-MS include drug detection, fire investigation, environmental analysis, explosives investigation,...
or liquid chromatography-mass spectrometry (LCMS) but can also use a variety of other analytical techniques.
Possible side-effects
- Loss of coordination
- Hallucinations (auditory and visual)
- Loss of sexual drive
- Swelling of prostate
- Loss of appetite
- Dilated pupils
- Increased heart rate
- ShakingTremorA tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
and muscle spasms - Chest pains
- Increased alertness
- Loss of any sleepiness
- Loss of stereoscopic vision
The effects shown above are not permanent.
Noscapine should not be taken with any MAOIs (monoamine oxidase inhibitors), as unknown and potentially fatal effects may occur.
Noscapine should not be taken in conjunction with warfarin. The anticoagulant effects of warfarin are drastically increased by noscapine, leading to serious and possibly fatal thinning of the blood.
External links
- http://www.pcref.org/MedInsight%20-%20PCREF%20Noscapine%20Review.pdf
- http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2291222 "Noscapine may increase the effects of warfarin"