Emetine
Encyclopedia
Emetine is a drug used as both an anti-protozoal and to induce vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...

. It is produced from the ipecac root.

Early emetine-based preparations

Early use of emetine was in the form of oral administration of the extract of ipecac root, or ipecacuanha. This extract was originally thought to contain only one 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...

, emetine, but was found to contain several, including cephaeline
Cephaeline
Cephaeline is an alkaloid chemical that induces vomiting by stimulating the stomach lining. It is found in commercial products such as syrup of ipecac...

, emetine, 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 to reduce nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

. Other suggestions to reduce nausea involved coating the drug to allow it to be released after digestion in the stomach.

Use of emetine as anti-amoebic

The identification of emetine as a more potent agent improved the treatment of amoebiasis
Amoebiasis
Entamebiasis is a term for the infection more commonly known as amoebiasis.It became the preferred term in MeSH in 1991, but the term amoebiasis is used by the World Health Organization and by those working in the field of amoebiasis research....

. 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
Mouth
The mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....

 administration.

Although it is a potent antiprotozoal, the drug also can interfere with muscle contractions, leading to cardiac failure in some cases. Because of this, in some uses it is required to be administered in a hospital environment so that adverse events can be addressed.

Dehydroemetine

Dehydroemetine
Dehydroemetine
Dehydroemetine is a synthetically produced antiprotozoal agent similar to emetine in its anti-amoebic properties and structure , but it produces fewer side effects...

 is a synthetically produced antiprotozoal agent
Antiprotozoal agent
Antiprotozoal agents is a class of pharmaceuticals used in treatment of protozoan infection.Protozoans have little in common with each other and so agents effective against one pathogen may not be effective against another...

 similar to emetine in its anti-amoebic properties and structure (they differ only in a double bond next to the ethyl radical), but it produces fewer side effects.

Cephaeline

Cephaeline
Cephaeline
Cephaeline is an alkaloid chemical that induces vomiting by stimulating the stomach lining. It is found in commercial products such as syrup of ipecac...

 is a desmethyl
Desmethyl
Desmethyl is a term used in organic chemistry to refer to a methyl group that has been removed.Examples include desmethyltramadol and desmethylsertraline....

 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 in eukaryotic 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.

Biosynthesis

The biosynthesis of cephaeline and emetine come from two main biosynthesis pathways: the biosynthesis of Dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 from L-tyrosine and the biosynthesis of secologanin
Secologanin
Secologanin is a monoterpene synthesized from geranyl pyrophosphate in the mevalonate pathway. Secologanin then proceedes with dopamine to form ipecac alkaloids.-Biosynthesis:...

 from geranyl diphosphate. Biosynthesis begins from the reaction between dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

 and secologanin
Secologanin
Secologanin is a monoterpene synthesized from geranyl pyrophosphate in the mevalonate pathway. Secologanin then proceedes with dopamine to form ipecac alkaloids.-Biosynthesis:...

 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
Cephaeline is an alkaloid chemical that induces vomiting by stimulating the stomach lining. It is found in commercial products such as syrup of ipecac...

 and a 6'-O-methylation successively to make emetine.

Side effects

Heavy or overusage of emetine can carry the risk of developing proximal myopathy
Myopathy
In medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...

 and/or cardiomyopathy
Cardiomyopathy
Cardiomyopathy, which literally means "heart muscle disease," is the deterioration of the function of the myocardium for any reason. People with cardiomyopathy are often at risk of arrhythmia or sudden cardiac death or both. Cardiomyopathy can often go undetected, making it especially dangerous to...

.
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