Noscapine (also known as Narcotine, Nectodon, Nospen, Anarcotine and (archaic) Opiane) is a
benzylisoquinoline
Substitution of the heterocycle isoquinoline at the C1 position by a benzyl group provides 1‑benzylisoquinoline, the most widely examined of the numerous benzylisoquinoline structural isomers. The 1-benzylisoquinoline moiety can be identified wi ...
alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...
, of the phthalideisoquinoline structural subgroup, which has been isolated from numerous species of the family
Papaveraceae
The Papaveraceae are an economically important family of about 42 genera and approximately 775 known species of flowering plants in the order Ranunculales, informally known as the poppy family. The family is cosmopolitan, occurring in temperat ...
(poppy family). It lacks significant hypnotic, euphoric, or analgesic effects affording it with very low addictive potential. This agent is primarily used for its
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-suppressing) effects.
Medical uses
Noscapine is often used as 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 ...
medication. A 2012 Dutch guideline, however, does not recommend its use for
acute
Acute may refer to:
Science and technology
* Acute angle
** Acute triangle
** Acute, a leaf shape in the glossary of leaf morphology
* Acute (medicine), a disease that it is of short duration and of recent onset.
** Acute toxicity, the adverse eff ...
cough
A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes. As a protective reflex, coughing can be repetitive with the cough reflex following three pha ...
ing.
Side effects
*Nausea
*Vomiting
*
Loss of coordination
Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
*
Hallucinations
A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinatio ...
(auditory and visual)
*
Loss of sexual drive
*
Swelling of prostate
*
Loss of appetite
Anorexia is a medical term for a loss of appetite. While the term in non-scientific publications is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while others i ...
*
Dilated pupils
Mydriasis is the dilation of the pupil, usually having a non-physiological cause, or sometimes a physiological pupillary response. Non-physiological causes of mydriasis include disease, trauma, or the use of certain types of drugs.
Normally, as ...
*
Increased heart rate
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 ...
*
Shaking and
muscle spasms
A spasm is a sudden involuntary contraction of a muscle, a group of muscles, or a hollow organ such as the bladder.
A spasmodic muscle contraction may be caused by many medical conditions, including dystonia. Most commonly, it is a muscle c ...
*Chest pains
*Increased alertness
*Loss of any sleepiness
*Loss of
stereoscopic vision
Stereopsis () is the component of depth perception retrieved through binocular vision.
Stereopsis is not the only contributor to depth perception, but it is a major one. Binocular vision happens because each eye receives a different image becaus ...
Interactions
Noscapine can increase the effects of centrally sedating substances such as alcohol and
hypnotic
Hypnotic (from Greek ''Hypnos'', sleep), or soporific drugs, commonly known as sleeping pills, are a class of (and umbrella term for) psychoactive drugs whose primary function is to induce sleep (or surgical anesthesiaWhen used in anesthesia ...
s.
The drug should not be taken with any
MAOI
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, especi ...
s (monoamine oxidase inhibitors), as unknown and potentially fatal effects may occur.
Noscapine should not be taken in conjunction with warfarin as the anticoagulant effects of warfarin may be increased.
Biosynthesis
The biosynthesis of noscapine in ''
P. somniferum
''Papaver somniferum'', commonly known as the opium poppy or breadseed poppy, is a species of flowering plant in the family Papaveraceae. It is the species of plant from which both opium and poppy seeds are derived and is also a valuable ornam ...
'' begins with
chorismic acid
Chorismic acid, more commonly known as its anionic form chorismate, is an important biochemical intermediate in plants and microorganisms. It is a precursor for:
* The aromatic amino acids phenylalanine, tryptophan, and tyrosine
* Indole, indole d ...
, which is synthesized via the
shikimate pathway
The shikimate pathway (shikimic acid pathway) is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (tryptophan, phenylalanine, and tyrosine). ...
from
erythrose 4-phosphate
Erythrose 4-phosphate is a phosphate of the simple sugar erythrose. It is an intermediate in the pentose phosphate pathway and the Calvin cycle.
In addition, it serves as a precursor in the biosynthesis of the aromatic amino acids tyrosine, pheny ...
and
phosphoenolpyruvate
Phosphoenolpyruvate (2-phosphoenolpyruvate, PEP) is the ester derived from the enol of pyruvate and phosphate. It exists as an anion. PEP is an important intermediate in biochemistry. It has the highest-energy phosphate bond found (−61.9 kJ/ ...
. Chorismic acid is a precursor to the amino acid
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
, the source of nitrogen in benzylisoquinoline alkaloids. Tyrosine can undergo a
PLP-mediated transamination to form
4-hydroxyphenylpyruvic acid
4-Hydroxyphenylpyruvic acid (4-HPPA) is an intermediate in the metabolism of the amino acid phenylalanine. The aromatic side chain of phenylalanine is hydroxylated by the enzyme phenylalanine hydroxylase to form tyrosine. The conversion from tyr ...
(4-HPP), followed by a
TPP-mediated decarboxylation to form
4-hydroxyphenylacetaldehyde
4-Hydroxyphenylacetaldehyde, also known as ''p''-hydroxyphenylacetaldehyde, is a natural product with the formula HOC6H4CH2CHO.
It is a derivative of phenylacetaldehyde and occurs as a white solid at room temperature.
Synthesis
4-Hydroxyphenyla ...
(4-HPAA). Tyrosine can also be hydroxylated to form
3,4-dihydroxyphenylalanine (DOPA), followed by a PLP-mediated decarboxylation to form
dopamine
Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
.
Norcoclaurine synthase (NCS) catalyzes a
Pictet-Spengler reaction between 4-HPAA and dopamine to synthesize (''S'')-
norcoclaurine
Higenamine (norcoclaurine) is a chemical compound found in a variety of plants including ''Nandina domestica'' (fruit), ''Aconitum carmichaelii'' (root), ''Asarum heterotropioides'', '' Galium divaricatum'' (stem and vine), ''Annona squamosa'', ...
, providing the characteristic benzylisoquinoline scaffold. (''S'')-Norcoclaurine is sequentially 6-''O''-methylated (6OMT), ''N''-methylated (CNMT), 3-hydroxylated (NMCH), and 4′-''O''-methylated (4′OMT), with the use of cofactors
S-adenosyl-methionine
''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...
(SAM) and
NADP
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NAD ...
+ for methylations and hydroxylations, respectively. These reactions produce (''S'')-
reticuline
Reticuline is a chemical compound found in a variety of plants including ''Lindera aggregata'', ''Annona squamosa'', and '' Ocotea fasciculata'' (also known as ''Ocotea duckei''). It is based on the benzylisoquinoline structure.
Reticuline is o ...
, a key branchpoint intermediate in the biosynthesis of benzylisoquinoline alkaloids.
The remainder of the noscapine biosynthetic pathway is largely governed by a single biosynthetic 10-gene cluster.
Genes comprising the cluster encode enzymes responsible for nine of the eleven remaining chemical transformations. First, berberine bridge enzyme (BBE), an enzyme not encoded by the cluster, forms the fused four-ring structure in (''S'')-
scoulerine
Scoulerine, also known as discretamine and aequaline, is a benzylisoquinoline alkaloid (BIA) that is derived directly from (''S'')-reticuline through the action of berberine bridge enzyme. It is a precursor of other BIAs, notably berberine, nosc ...
. BBE uses O
2 as an oxidant and is aided by cofactor
flavin adenine dinucleotide
Flavin may refer to:
Placename
* Flavin, Aveyron, a commune in southern France
Surname
* Adrian Flavin (born 1979), a professional rugby player
* Christopher Flavin, president of the Worldwatch Institute
* Dan Flavin (1933–1996), a minimalis ...
(FAD). Next, an ''O''-methyltransferase (SOMT) methylates the 9-hydroxyl group. Canadine synthase (CAS) catalyzes the formation of a unique C2-C3 methylenedioxy bridge in (''S'')-canadine.
An ''N''-methylation (TNMT) and two hydroxylations (CYP82Y1, CYP82X2) follow, aided by SAM and O
2/NADPH, respectively. The C13 alcohol is then acetylated by an acetyltransferase (AT1) using
acetyl-CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...
. Another
cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
enzyme (CYP82X1) catalyzes the hydroxylation of C8, and the newly formed hemiaminal spontaneously cleaves, yielding a tertiary amine and aldehyde. A methyltransferase heterodimer (OMT2:OMT3) catalyzes a SAM-mediated ''O''-methylation on C4′.
The ''O''-acetyl group is then cleaved by a carboxylesterase (CXE1), yielding an alcohol which immediately reacts with the neighboring C1 aldehyde to form a hemiacetal in a new five-membered ring. The apparent counteractivity between AT1 and CXE1 suggests that acetylation in this context is employed as a protective group, preventing hemiacetal formation until the ester is enzymatically cleaved.
Finally, an
NAD+-dependent
short-chain dehydrogenase
The short-chain dehydrogenases/reductases family (SDR) is a very large family of enzymes, most of which are known to be NAD- or NADP-dependent oxidoreductases. As the first member of this family to be characterised was Drosophila alcohol dehydroge ...
(NOS) oxidizes the hemiacetal to a lactone, completing noscapine biosynthesis.
Mechanism of action
Noscapine's antitussive effects appear to be primarily mediated by its
σ–receptor agonist activity. Evidence for this mechanism is suggested by experimental evidence in rats. Pretreatment with
rimcazole
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 phencyclidine and cocaine, and rimcazole was ori ...
, a σ-specific
antagonist
An antagonist is a character in a story who is presented as the chief foe of the protagonist.
Etymology
The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...
, causes a dose-dependent reduction in antitussive activity of noscapine.
Noscapine, and its synthetic derivatives called noscapinoids, are known to interact with microtubules and inhibit cancer cell proliferation
Structure analysis
The
lactone
Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring.
Lactones are formed by intramolecular esterification of the co ...
ring is unstable and opens in basic media. The opposite reaction is presented in acidic media. The bond (C1−C3′) connecting the two optically active carbon atoms is also unstable. In aqueous solution of
sulfuric acid
Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...
and heating it dissociates into
cotarnine (4-methoxy-6-methyl-5,6,7,8-tetrahydro-
,3ioxolo
,5-''g''soquinoline) and
opic acid (6-formyl-2,3-dimethoxybenzoic acid). When noscapine is reduced with
zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
/
HCl HCL may refer to:
Science and medicine
* Hairy cell leukemia, an uncommon and slowly progressing B cell leukemia
* Harvard Cyclotron Laboratory, from 1961 to 2002, a proton accelerator used for research and development
* Hollow-cathode lamp, a spe ...
, the bond C1−C3′ saturates and the molecule dissociates into
hydrocotarnine (2-hydroxycotarnine) and
meconine (6,7-dimethoxyisobenzofuran-1(3''H'')-one).
History
Noscapine was first isolated and characterized in chemical breakdown and properties in 1803 under the denomination of "Narcotine" by Jean-Francois Derosne, a French chemist in Paris. Then
Pierre-Jean Robiquet
Pierre Jean Robiquet (13 January 1780 – 29 April 1840) was a French chemist. He laid founding work in identifying amino acids, the fundamental building blocks of proteins. He did this through recognizing the first of them, asparagine, in 1806 ...
, another French chemist, proved narcotine and morphine to be distinct alkaloids in 1831. Finally, Pierre-Jean Robiquet conducted over 20 years between 1815 and 1835 a series of studies in the enhancement of methods for the isolation of
morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
, and also isolated in 1832 another very important component of raw opium, that he called
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 ...
, currently a widely used opium-derived
compound
Compound may refer to:
Architecture and built environments
* Compound (enclosure), a cluster of buildings having a shared purpose, usually inside a fence or wall
** Compound (fortification), a version of the above fortified with defensive struct ...
.
Society and culture
Recreational use
There are anecdotal reports of the recreational use of
over-the-counter drug
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
A prescription drug (also prescription medication or prescripti ...
s in several countries, being readily available from local pharmacies without a prescription. The effects, beginning around 45 to 120 minutes after consumption, are similar to
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 ...
and
alcohol intoxication
Alcohol intoxication, also known as alcohol poisoning, commonly described as drunkenness or inebriation, is the negative behavior and physical effects caused by a recent consumption of alcohol. In addition to the toxicity of ethanol, the main p ...
. Unlike dextromethorphan, noscapine is not an
NMDA receptor antagonist
NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...
.
Noscapine in heroin
Noscapine can survive the manufacturing processes of
heroin
Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brow ...
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
Liège ( , , ; wa, Lîdje ; nl, Luik ; german: Lüttich ) is a major city and municipality of Wallonia and the capital of the Belgian province of Liège.
The city is situated in the valley of the Meuse, in the east of Belgium, not far from b ...
,
Belgium
Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...
, 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
Heroin, also known as diacetylmorphine and diamorphine among other names, is a potent opioid mainly used as a recreational drug for its euphoric effects. Medical grade diamorphine is used as a pure hydrochloride salt. Various white and brown ...
.
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 is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra.
Cel ...
samples alongside noscapine include
papaverine
Papaverine (Latin ''papaver'', "poppy") is an opium alkaloid antispasmodic drug, used primarily in the treatment of visceral spasms and vasospasms (especially those involving the intestines, heart, or brain), occasionally in the treatment of erec ...
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 is one of the four fundamental states of matter (the others being solid, liquid, and plasma).
A pure gas may be made up of individual atoms (e.g. a noble gas like neon), elemental molecules made from one type of atom (e.g. oxygen), or com ...
or liquid chromatography-mass spectrometry (LCMS) but can also use a variety of other analytical techniques.
Research
Clinical Trials
The efficacy of noscapine in the treatment of certain
hematological
Hematology ( always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the produc ...
malignancies has been explored in the clinic.
Polyploidy
Polyploidy is a condition in which the cells of an organism have more than one pair of ( homologous) chromosomes. Most species whose cells have nuclei ( eukaryotes) are diploid, meaning they have two sets of chromosomes, where each set contain ...
induction by noscapine has been observed ''in vitro'' in human lymphocytes at high dose levels (>30 μM); however, low-level systemic exposure, e.g. with cough medications, does not appear to present a genotoxic hazard. The mechanism of
polyploidy
Polyploidy is a condition in which the cells of an organism have more than one pair of ( homologous) chromosomes. Most species whose cells have nuclei ( eukaryotes) are diploid, meaning they have two sets of chromosomes, where each set contain ...
induction by noscapine is suggested to involve either chromosome
spindle apparatus
In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a pr ...
damage or cell fusion.
Noscapine Biosynthesis Reconstitution
Many of the enzymes in the noscapine biosynthetic pathway was elucidated by the discovery of a 10 gene "operon-like cluster" named HN1.
In 2016, the biosynthetic pathway of noscapine was reconstituted in yeast cells, allowing the drug to be synthesised without the requirement of harvest and purification from plant material. In 2018, the entire noscapine pathway was reconstituted and produced in yeast from simple molecules. In addition, protein expression was optimised in yeast, allowing production of noscapine to be improved 18,000 fold. It is hoped that this technology could be used to produce pharmaceutical alkaloids such as noscapine which are currently expressed at too low a yield ''in plantae'' to be mass-produced, allowing them to become marketable therapeutic drugs.
Anticancer derivatives
Noscapine is itself an anti-mitiotic agent, therefore its analogs have great potential as novel anti-cancer drugs.
Analogs having significant
cytotoxic
Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa'').
Cell physiology
Treating cells ...
effects through modified
1,3-benzodioxole moiety have been developed.
Similarly, N-alkyl amine, 1,3-diynyl, 9-vinyl-phenyl and 9-arylimino derivatives of noscapine have also been developed.
Their mechanism of action is through
tubulin inhibition.
Anti-Inflammatory Effects
Interestingly, various studies have indicated that noscapine has anti-inflammatory effects and significantly reduces the levels of proinflammatory factors such as interleukin 1β (IL-1β), IFN-c, and IL-6. In this regard, in another study, Khakpour et al. examined the effect of noscapine against carrageenan-induced inflammation in rats. They found that noscapine at a dose of 5 mg/kg body weight in three hours after the injection has the most antiinflammatory effects. Moreover, they showed that the amount of inflammation reduction at this dose of noscapine is approximately equal to the indomethacin as a known and standard anti-inflammatory medication. Furthermore, Shiri et al. concluded that noscapine prevented the progression of bradykinin-induced inflammation in the rat’s foot by antagonising bradykinin receptors. In addition, Zughaier et al. evaluated the anti-inflammatory effects of brominated noscapine. The brominated form of noscapine has been shown to inhibit the secretion of the cytokine TNF-α and the chemokine IP-10/CXCL10 from macrophages, thereby reducing inflammation without affecting macrophage survival. Furthermore, the bromated derivative of noscapine has about 5 to 40 times more potent effects than noscapine. Again, this brominated derivative also inhibits toll-like receptor (TLR), tumour necrosis factor α (TNF-α), and NO in human and mous macrophages without causing toxicity. Furthermore, brominated noscapine has potent anti-inflammatory activity in models of septic inflammation, inhibits inflammatory factors in a dose-dependent manner, and prevents the release of TNF-α and NO in human and mouse macrophages. Another study on inflammatory bowel disease (ulcerative colitis) and colon cancer found that noscapine had an excellent anti-inflammatory effect that could significantly decrease the levels of proinflammatory factors such as IL-1β, IFN-c, and IL-6, compared to the control group. Additionally, it has been found that chitosan nanoparticles containing brominated noscapine derivatives could reduce proinflammatory cytokines such as IL-1β, IFN-c, and IL-6 and inflammation within colon mucosal tissue.
See also
*
Cough syrup
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 ...
*
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 ...
;
Pholcodine
Pholcodine is an opioid cough suppressant (antitussive). It helps suppress unproductive coughs and also has a mild sedative effect, but has little or no analgesic effects. It is also known as morpholinylethylmorphine and homocodeine.
Pholcodine is ...
*
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 ...
;
Dimemorfan
Dimemorfan (INN) (or dimemorphan) (brand names Astomin, Dastosirr, Tusben), or dimemorfan phosphate (JAN), also known as 3,17-dimethylmorphinan, is an antitussive (cough suppressant) of the morphinan family that is widely used in Japan and is als ...
*
Racemorphan
Racemorphan, or morphanol, is the racemic mixture of the two stereoisomers of 17-methylmorphinan-3-ol, each with differing pharmacology and effects:
* Dextrorphan - an antitussive and dissociative hallucinogen ( NMDA receptor antagonist)
* L ...
;
Dextrorphan
Dextrorphan (DXO) is a psychoactive drug of the morphinan class which acts as an antitussive or cough suppressant and dissociative hallucinogen. It is the dextrorotatory enantiomer of racemorphan; the levorotatory enantiomer is levorphanol. Dext ...
;
Levorphanol
Levorphanol (brand name Levo-Dromoran) is an opioid medication used to treat moderate to severe pain. It is the levorotatory enantiomer of the compound racemorphan. Its dextrorotatory counterpart is dextrorphan.
It was first described in German ...
*
Butamirate
Butamirate (or brospamin, trade names Acodeen, Codesin, Pertix, Sinecod, Sinecoden, Sinecodix) is a cough suppressant. It has been marketed in Europe and Mexico, but not in the United States.
As the citrate salt, it is sold in the form of lozenge ...
*
Pentoxyverine
Pentoxyverine (rINN) 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 medicatio ...
*
Tipepidine
Tipepidine (INN) (brand names Asverin, Antupex, Asvelik, Asvex, Bitiodin, Cofdenin A, Hustel, Nodal, Sotal), also known as tipepidine hibenzate (JAN), is a synthetic, non-opioid antitussive and expectorant of the thiambutene class. It acts as an ...
*
Cloperastine
Cloperastine (INN) or cloperastin, in the forms of cloperastine hydrochloride ( JAN) (brand names Hustazol, Nitossil, Seki) and cloperastine fendizoate (or hybenzoate), is an antitussive and antihistamine that is marketed as a cough suppressant ...
*
Levocloperastine
*
Narceine, a lesser known but related opium alkaloid.
References
{{Sigma receptor modulators
Natural opium alkaloids
Antitussives
3-(5,6,7,8-tetrahydro-(1,3)dioxolo(4,5-g)isoquinolin-5-yl)-3H-2-benzofuran-1-ones
Pyrogallol ethers
Sigma agonists