Emetine

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Emetine
QP51AX02 (WHO
)
Identifiers
  • (2S,3R,11bS)-2-{[(1R)-6,7-Dimethoxy-1,2,3,4-
    tetrahydroisoquinolin-1-yl]methyl}-3-ethyl-9,10-
    dimethoxy-2,3,4,6,7,11b-hexahydro-1H-pyrido
    [2,1-a]isoquinoline
JSmol)
Melting point74 °C (165 °F)
  • O(c1cc2c(cc1OC)[C@H](NCC2)C[C@H]5C[C@H]4c3c(cc(OC)c(OC)c3)CCN4C[C@@H]5CC)C
  • InChI=1S/C29H40N2O4/c1-6-18-17-31-10-8-20-14-27(33-3)29(35-5)16-23(20)25(31)12-21(18)11-24-22-15-28(34-4)26(32-2)13-19(22)7-9-30-24/h13-16,18,21,24-25,30H,6-12,17H2,1-5H3/t18-,21-,24+,25-/m0/s1 checkY
  • Key:AUVVAXYIELKVAI-CKBKHPSWSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Emetine is a drug used as both an

emetic properties.[1]

Early preparations

Mechanism of action of emetine was studied by François Magendie during the nineteenth century.[citation needed]

Early use of emetine was in the form of oral administration of the extract of

opioids to reduce nausea. Other approaches to reduce nausea involved coated tablets, allowing the drug to be released after digestion in the stomach.[2]

Use as anti-amoebic

The identification of emetine as a more potent agent improved the treatment of amoebiasis. 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 administration.[citation needed]

Although it is a potent antiprotozoal, the drug also can interfere with muscle contractions, leading to

cardiac failure in some cases. [citation needed
] Because of this, in some uses it is required to be administered in a hospital so that adverse events can be addressed.

Dehydroemetine

Main article: dehydroemetine

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

Cephaeline

Main article: cephaeline

desmethyl
analog of emetine also found in ipecac root.

Use in blocking protein synthesis

Emetine dihydrochloro hydrate is used in the laboratory to block

eukaryotic cells. It does this by binding to the 40S subunit of the ribosome.[3] 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),[4][5] and they exhibit cross-resistance to cryptopleurine, tylocrebrine, cephaeline and tubulosine, but not other inhibitors of protein synthesis.[6] 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.[7]

Biosynthesis

Proposed biosynthesis of emetine

The biosynthesis of cephaeline and emetine come from two main biosynthesis pathways: the biosynthesis of

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 and a 6'-O-methylation successively to make emetine.[8][9]

Side effects

Heavy or overusage of emetine can carry the risk of developing proximal myopathy and/or cardiomyopathy.[10]

Research

A 2018 study

endosomes 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.[12]

In 2016, a study[13] found that low doses of emetine inhibited cytomegalovirus replication and was synergistic with ganciclovir.

References

  1. ^ "NCATS Inxight: Drugs". drugs.ncats.io. Retrieved 2020-01-22.
  2. ^ Cushny AR (1918). A Textbook of pharmacology and therapeutics, or the action of drugs in health and disease. Lea and Febiger, New York. pp. 438–442. emetine.
  3. PMID 334249
    .
  4. S2CID 38874641
    .
  5. PMID 3839563
    .
  6. PMID 560858
    .
  7. PMID 7412757
    .
  8. PMID 21228475
    .
  9. PMID 20061395
    .
  10. ^ "NCATS Inxight: Drugs". drugs.ncats.io. Retrieved 2020-01-22.
  11. PMID 30028873
    .
  12. ^ "How rabies virus moves through nerve cells, and how it might be stopped".
  13. PMID 27336364
    .
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