Emetine is a drug used as both an
anti-protozoal
Antiprotozoal agents ( ATC code: ATC P01) is a class of pharmaceuticals used in treatment of protozoan infection.
A paraphyletic group, protozoans have little in common with each other. For example, ''Entamoeba histolytica'', a unikont eukaryoti ...
and to induce
vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
. It is produced from the
ipecac root. It takes its name from its
emetic
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
properties.
Early preparations
Mechanism of action of emetine was studied by
François Magendie
__NOTOC__
François Magendie (6 October 1783 – 7 October 1855) was a French physiologist, considered a pioneer of experimental physiology. He is known for describing the foramen of Magendie. There is also a ''Magendie sign'', a downward a ...
during the nineteenth century.
Early use of emetine was in the form of oral administration of the extract of
ipecac
Syrup of ipecac (), or simply ipecac, is a drug that was once widely used as an expectorant (in low doses) and a rapid-acting emetic (in higher doses). It is obtained from the dried rhizome and roots of the ipecacuanha plant (''Carapichea ipecac ...
root, or ipecacuanha. This extract was originally thought to contain only one
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 ...
, emetine, but was found to contain several, including
cephaeline
Cephaeline is an alkaloid that is found in '' Cephaelis ipecacuanha'' and other plant species including '' Psychotria acuminata''. Cephaeline induces vomiting by stimulating the stomach lining and is found in commercial products such as syrup of ...
,
psychotrine and others. Although this therapy was reportedly successful, the extract caused vomiting in many patients, which reduced its utility. In some cases, it was given with
opioids
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 use ...
to reduce
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
. Other approaches to reduce nausea involved coated tablets, allowing the drug to be released after digestion in the stomach.
Use as anti-amoebic
The identification of emetine as a more potent agent improved the treatment of
amoebiasis
Amoebiasis, or amoebic dysentery, is an infection of the intestines caused by a parasitic amoeba ''Entamoeba histolytica''. Amoebiasis can be present with no, mild, or severe symptoms. Symptoms may include lethargy, loss of weight, colonic ulce ...
. While use of emetine still caused nausea, it was more effective than the crude extract of ipecac root. Additionally, emetine could be administered hypodermically which still produced nausea, but not to the degree experienced in
oral
The word oral may refer to:
Relating to the mouth
* Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid
**Oral administration of medicines
** Oral examination (also known as an oral exam or or ...
administration.
Although it is a potent antiprotozoal, the drug also can interfere with muscle contractions, leading to
cardiac failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, an ...
in some cases. Because of this, in some uses it is required to be administered in a hospital so that adverse events can be addressed.
Dehydroemetine
Dehydroemetine
Dehydroemetine is a synthetically produced antiprotozoal agent similar to emetine in its anti-amoebic properties and structure (they differ only in a double bond next to the ethyl substituent), but it produces fewer side effects. In the United S ...
is a synthetically produced
antiprotozoal agent
Antiprotozoal agents ( ATC code: ATC P01) is a class of pharmaceuticals used in treatment of protozoan infection.
A paraphyletic group, protozoans have little in common with each other. For example, ''Entamoeba histolytica'', a unikont eukaryotic ...
similar to emetine in its anti-amoebic properties and structure (they differ only in a
double bond
In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...
next to the
ethyl group
In organic chemistry, an ethyl group (abbr. Et) is an alkyl substituent with the formula , derived from ethane (). ''Ethyl'' is used in the International Union of Pure and Applied Chemistry's nomenclature of organic chemistry for a saturated ...
), but it produces fewer side effects.
Cephaeline
Cephaeline
Cephaeline is an alkaloid that is found in '' Cephaelis ipecacuanha'' and other plant species including '' Psychotria acuminata''. Cephaeline induces vomiting by stimulating the stomach lining and is found in commercial products such as syrup of ...
is a
desmethyl In chemical nomenclature, nor- is a prefix to name a structural analog that can be derived from a parent compound by the removal of one carbon atom along with the accompanying hydrogen atoms. The nor-compound can be derived by removal of a , , or ...
analog of emetine also found in ipecac root.
Use in blocking protein synthesis
Emetine dihydrochloro hydrate is used in the laboratory to block
protein synthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
in
eukaryotic
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...
cells. It does this by binding to the 40S subunit of the ribosome.
This can thus be used in the study of protein degradation in cells. Mutants resistant to emetine are altered in the 40S ribosomal subunit (S14 protein),
and they exhibit cross-resistance to cryptopleurine, tylocrebrine,
cephaeline
Cephaeline is an alkaloid that is found in '' Cephaelis ipecacuanha'' and other plant species including '' Psychotria acuminata''. Cephaeline induces vomiting by stimulating the stomach lining and is found in commercial products such as syrup of ...
and tubulosine, but not other inhibitors of protein synthesis.
The compounds to which these mutants exhibit cross-resistance have been shown to share common structural determinants with emetine that are responsible for their biological activities.
Biosynthesis
![Emetine biosynthesis resized](https://upload.wikimedia.org/wikipedia/commons/1/17/Emetine_biosynthesis_resized.png)
The biosynthesis of cephaeline and emetine come from two main biosynthesis pathways: the biosynthesis of
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 ...
from
L-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 ...
and the biosynthesis of
secologanin
Secologanin is a secoiridoid monoterpene synthesized from geranyl pyrophosphate in the mevalonate pathway. Secologanin then proceeds with dopamine or tryptamine to form ipecac and terpene indole alkaloids, respectively.
Biosynthesis
Secologanin ...
from
geranyl diphosphate
Geranyl pyrophosphate (GPP), also known as geranyl diphosphate (GDP), is the pyrophosphate ester of the terpenoid geraniol. Its salts are colorless. It is a precursor to many natural products.
Occurrence
GPP is an intermediate in the isoprenoid ...
. Biosynthesis begins from the reaction between
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 ...
and
secologanin
Secologanin is a secoiridoid monoterpene synthesized from geranyl pyrophosphate in the mevalonate pathway. Secologanin then proceeds with dopamine or tryptamine to form ipecac and terpene indole alkaloids, respectively.
Biosynthesis
Secologanin ...
forming N-deacetylisoipecoside (S-form) and N-deacetylipecoside (R-form). The S-form then goes through a
Pictet-Spengler type reaction followed by a series of O-methylations and the removal of glucose, with O-methyltransferases and a glycosidase, to form proemetine. Proemetine then reacts with another dopamine molecule to form 7'-O-demethylcephaeline. The final products are then produced with a 7'-O-methylation to make
cephaeline
Cephaeline is an alkaloid that is found in '' Cephaelis ipecacuanha'' and other plant species including '' Psychotria acuminata''. Cephaeline induces vomiting by stimulating the stomach lining and is found in commercial products such as syrup of ...
and a 6'-O-methylation successively to make emetine.
Side effects
Heavy or overusage of emetine can carry the risk of developing proximal
myopathy
In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This meani ...
and/or
cardiomyopathy
Cardiomyopathy is a group of diseases that affect the heart muscle. Early on there may be few or no symptoms. As the disease worsens, shortness of breath, feeling tired, and swelling of the legs may occur, due to the onset of heart failure. A ...
.
Research
A 2018 study at
Princeton University
Princeton University is a private university, private research university in Princeton, New Jersey. Founded in 1746 in Elizabeth, New Jersey, Elizabeth as the College of New Jersey, Princeton is the List of Colonial Colleges, fourth-oldest ins ...
and
Thomas Jefferson University
Thomas Jefferson University is a private research university in Philadelphia, Pennsylvania. Established in its earliest form in 1824, the university officially combined with Philadelphia University in 2017. To signify its heritage, the univer ...
has demonstrated that emetine blocks the dissemination of
rabies virus
Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
inside nerve cells, but the exact mechanism is still under investigation. Emetine had no effect on the transport of
endosomes
Endosomes are a collection of intracellular sorting organelles in eukaryotic cells. They are parts of endocytic membrane transport pathway originating from the trans Golgi network. Molecules or ligands internalized from the plasma membrane can ...
devoid of the rabies virus. (Rabies resides in nerve endosomes). But endosomes carrying the virus were either completely immobilized, or were only able to move short distances at slower-than-normal speeds.
In 2016, a study
found that low doses of emetine inhibited
cytomegalovirus
''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
replication and was synergistic with
ganciclovir
Ganciclovir, sold under the brand name Cytovene among others, is an antiviral medication used to treat cytomegalovirus (CMV) infections.
Ganciclovir was patented in 1980 and approved for medical use in 1988.
Medical use
Ganciclovir is indicated ...
.
References
{{Agents against amoebozoa
Antiprotozoal agents
Isoquinoline alkaloids
Norsalsolinol ethers
Emetics
Protein synthesis inhibitors