Emetine inhibiting protein synthesis

Emetine and dehydroemetine are natural alkaloid obtained from Cephaelis ipecacuanha and synthetic analog respectively. They are effective against tissue trophozoites of . histolytica. It has no effect on cysts but effective in amoebic liver abscess also. It acts by inhibiting protein synthesis by arresting intraribosome translocation of tRNA-amino acid complex. Dehydroemetine is less toxic than emetine and very effective drug for tissue amoebiasis. It is more rapidly eliminated from the body than emetine. 

Emetine [EM e teen] and dehydroemetine [de hye dro EM e teen] are alternate agents for the treatment of amebiasis. They inhibit protein synthesis by blocking chain elongation1. Intramuscular injection is the preferred route. Emetine is concentrated in the liver where it persists for a month after a single dose. It is slowly metabolized and excreted and can accumulate. Its ty2 is 5 days. The use of these ipecac alkaloids is limited by their toxicities. Dehydroemetine is probably less toxic than emetine. Close clinical observation is necessary when these drugs are used. Among the untoward effects are pain at the site of injection, transient nausea, cardiotoxicity (e.g., arrhythmias, congestive heart failure), neuromuscular weakness, dizziness, and rashes. 

Emetine and dehydroemetine exert a direct aniebicidal action on various forms nf E. Iihwlyiica. They arc protoplasmic poisons that inhibit protein synthesis in pnilo/iKil and mammalian cells by preventing protein elongation. Because their effect in intestinal amebiasis is solely. symptom-... 

Early mechanistic studies in the 1960s demonstrated that tylophorine alkaloids irreversibly inhibit DNA synthesis and affected protein synthesis at the elongation stage of the translation cycle [84], In HeLa cells, tylophorine (1) reversibly inhibits RNA synthesis and irreversibly inhibits DNA synthesis, but a predominant effect is exerted on protein synthesis and elongation of peptide ehains by preventing breakdown of polyribosomes and release of nascent peptides. Tyloerebrinc (2) was shown to have equivalent activity to emetine on inhibition of protein synthesis in Entamoeba histolytica [85]. Tylophorine and tylocrebrine were also found to inhibit protein synthesis in Ehrlich ascites cells and... 

Emetine (Fig. 7-9) in the form of the crude drug obtained from the roots and rhizomes of Ipecac (Cephaelis ipecacuanha) has been in use since the seventeenth century. The alkaloid, as the hydrochloride, has been used parenterally to treat amebic dysentery. It is also effective in hepatic infestation, but not against amebic cysts. Because of its cardiac toxicity and emetogenic properties, it has been superseded by metronidazole and chloroquine, but it is still used as an alternative. The amebicidal mechanism of emetine is protein synthesis inhibition by interference of peptidyl-RNA translocation. Since this action is general to eukaryotic cells, its relative selectivity in the presence of mammalian cells is not well understood. Unrelated uses of Ipecac (presumably due to its alkaloid content) are as an expectorant in cough preparations and an emergency emetic (Syrup of Ipecac). 

Emetine and cycloheximide are two molecules that look quite dissimilar at first glance, but have conformationally similar areas which cause both of them to inhibit protein synthesis in the ribosomes of most living cells (Section 4.1, P-147). 

This drug has a direct amebicidal effect against trophozoites E. histolytica in tissues, and it is not active against cysts in either the lumen or intestinal walls, or in other organs. The mechanism of action of emetine consists of the blockage of protein synthesis in eukaryotic (but not in prokaryotic) cells. It inhibits the process of polypeptide chain formation. Protein synthesis is inhibited in parasite and mammalian cells, but not in bacteria. 

Emetine and cephaeline are both potent inhibitors of protein synthesis, inhibiting at the translocation stage. They display antitumour and antiviral as well as antiamoebic activity, but are too toxic for therapeutic use. In recent studies, O-methylpsychotrine has displayed fairly low effects on protein synthesis, but a quite potent ability to curb viral replication through inhibition of HIV-reverse transcriptase. This may give it potential in the treatment of AIDS. 

Leatherman DL, Middlebrook JL. Effect of emetine on T-2 toxin-induced inhibition of protein synthesis in mammalian cells. J Pharmacol Exp Ther. 1993 266(2) 741 -748. 

C. Chronic repeated dosing. The emetine component causes inhibition of protein synthesis that is particularly demonstrated in human myocytes and skeletal muscle cells after overdose or prolonged use. Another proposed mechanism for cellular toxicity includes blockade of sodium and calcium channels. 

Emetine is a strong inhibitor of protein synthesis, functioning through prevention of the translation of amino-acyl transfer RNA to ribosomal peptide. It also inhibits in vitro aerobic glycolysis in cardiac muscle. 

Emetine - As an inhibitor of protein synthesis at the transcription level, emetine is also active against leukemias L-1210 and P-388, B16 melanomas, Ehrlich ascites carcinoma and Yoshida sarcoma. Pharmacologic studies showed that it effects a sympathetic blockade, antagonizes hyal-uronldase, inhibits oxydative N-demethylatlon of aminopyrine and N-ethyl-morphlne as well as the S-demethylation of 6-MP riboside in vitro. 2,143... 

Administered intramuscularly, dehydroemetlne (VIII) is reported to be less cardiotoxlc than emetine. Recent reports have attested to the effectiveness f oral dehydroemetine in intestinal and extra-intestinal amebiasis. Further support for the mechanism of action of emetine involving Inhibition of protein synthesis is discussed by Grollman. 9 e advantages of chloroquine, which is still one of the drugs of choice in the treatment of systemic amebiasis, are its oral use and lack of cardiac toxicity. Other drugs which have been shown to be intestinal and systemic... 

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