Dehydroemetine

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Dehydroemetine
Dehydroemetine.png
Clinical data
AHFS/Drugs.com International Drug Names
ATC code
Identifiers
  • (11bS)-2-[[(1R)-6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-1-yl]methyl]-3-ethyl-9,10-dimethoxy-4,6,7,11b-tetrahydro-1H-pyrido[2,1-a]isoquinoline
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.023.220 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C29H38N2O4
Molar mass 478.633 g·mol−1
3D model (JSmol)
  • O(c1cc2c(cc1OC)[C@H](NCC2)CC\5=C(/CC)CN4[C@H](c3c(cc(OC)c(OC)c3)CC4)C/5)C
  • InChI=1S/C29H38N2O4/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/h13-16,24-25,30H,6-12,17H2,1-5H3/t24-,25+/m1/s1 X mark.svgN
  • Key:XXLZPUYGHQWHRN-RPBOFIJWSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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 States, it is manufactured by Roche.[ citation needed ]

Contents

Mechanism

Its exact mechanism is not known, but in vitro it inhibits translocation. [1]

Uses

It was at one-time, but is no longer distributed by the Center for Disease Control on a compassionate use basis as an investigational drug for the treatment of metronidazole-resistant amoebiasis. [2]

Amoebic infections

Some examples of the use of dehydroemetine in the treatment of amoebic infections include:

  1. In 1993, the successful treatment of cutaneous amebiasis in a 7-year-old girl with dehydroemetine and metronidazole in Mexico. [3]
  2. A double-blind study of oral dehydroemetine in the treatment of amoebiasis performed at St. Mary's Hospital, Catholic Medical College, Seoul, Republic of Korea in 1973-1974 showed dehydroemetine treatment was effective. A total of 60 patients were treated, 20 with dehydroemetine, 20 with Tiberal, and 20 with metronidazole. One-fourth of the patients treated with dehydroemetine reported adverse reactions, compared to 20% with other drugs, but no patient discontinued therapy due to the reaction. In all three cases, the drug therapy resulted in clearance of the infection, defined as negative results through an O&P exam, in all but 1-2 patients. [4]
  1. A 1979 study of 27 patients treated with dehydroemetine and various other drugs suggested all drug combinations were successful at treating amoebic liver abscesses. [5]
  2. A 1986 in vitro study compared the effects of dehydroemetine, metronidazole, ornidazole, and secnidazole on Entamoeba histolytica . Metronidazole was found to be most effective, and the other three drugs were of similar effectiveness. [6]

In other diseases

A 2020 in-vitro study found dehydroemetine to be effective in malaria. [7]

A 1980 report described the use of dehydroemetine in treatment of herpes zoster, a condition which can produce painful neurological symptoms. The study involved 40 patients, all of whom were over 60, and compared dehydroemetine treatment to another drug. The study reported patients treated with dehydroemetine experienced relief of neuralgia with no changes in cardiovascular functions. [8]

Dehydroemetine has been investigated as a treatment for Leishmania infection. [9]

Related Research Articles

<i>Entamoeba</i> Genus of internal parasites

Entamoeba is a genus of Amoebozoa found as internal parasites or commensals of animals. In 1875, Fedor Lösch described the first proven case of amoebic dysentery in St. Petersburg, Russia. He referred to the amoeba he observed microscopically as Amoeba coli; however, it is not clear whether he was using this as a descriptive term or intended it as a formal taxonomic name. The genus Entamoeba was defined by Casagrandi and Barbagallo for the species Entamoeba coli, which is known to be a commensal organism. Lösch's organism was renamed Entamoeba histolytica by Fritz Schaudinn in 1903; he later died, in 1906, from a self-inflicted infection when studying this amoeba. For a time during the first half of the 20th century the entire genus Entamoeba was transferred to Endamoeba, a genus of amoebas infecting invertebrates about which little is known. This move was reversed by the International Commission on Zoological Nomenclature in the late 1950s, and Entamoeba has stayed 'stable' ever since.

<span class="mw-page-title-main">Metronidazole</span> Antibiotic and antiprotozoal medication

Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is effective for dracunculiasis, giardiasis, trichomoniasis, and amebiasis. It is an option for a first episode of mild-to-moderate Clostridium difficile colitis if vancomycin or fidaxomicin is unavailable. Metronidazole is available orally, as a cream or gel, and by slow intravenous infusion.

<i>Entamoeba histolytica</i> Anaerobic parasitic protist

Entamoeba histolytica is an anaerobic parasitic amoebozoan, part of the genus Entamoeba. Predominantly infecting humans and other primates causing amoebiasis, E. histolytica is estimated to infect about 35-50 million people worldwide. E. histolytica infection is estimated to kill more than 55,000 people each year. Previously, it was thought that 10% of the world population was infected, but these figures predate the recognition that at least 90% of these infections were due to a second species, E. dispar. Mammals such as dogs and cats can become infected transiently, but are not thought to contribute significantly to transmission.

<span class="mw-page-title-main">Amoebozoa</span> Phylum of protozoans

Amoebozoa is a major taxonomic group containing about 2,400 described species of amoeboid protists, often possessing blunt, fingerlike, lobose pseudopods and tubular mitochondrial cristae. In traditional classification schemes, Amoebozoa is usually ranked as a phylum within either the kingdom Protista or the kingdom Protozoa. In the classification favored by the International Society of Protistologists, it is retained as an unranked "supergroup" within Eukaryota. Molecular genetic analysis supports Amoebozoa as a monophyletic clade. Modern studies of eukaryotic phylogenetic trees identify it as the sister group to Opisthokonta, another major clade which contains both fungi and animals as well as several other clades comprising some 300 species of unicellular eukaryotes. Amoebozoa and Opisthokonta are sometimes grouped together in a high-level taxon, variously named Unikonta, Amorphea or Opimoda.

<span class="mw-page-title-main">Clioquinol</span> Medication

Clioquinol (iodochlorhydroxyquin) is an antifungal drug and antiprotozoal drug. It is neurotoxic in large doses. It is a member of a family of drugs called hydroxyquinolines which inhibit certain enzymes related to DNA replication. The drugs have been found to have activity against both viral and protozoal infections.

<span class="mw-page-title-main">Famciclovir</span> Chemical compound

Famciclovir is a guanosine analogue antiviral drug used for the treatment of various herpesvirus infections, most commonly for herpes zoster (shingles). It is a prodrug form of penciclovir with improved oral bioavailability. Famciclovir is marketed under the trade name Famvir (Novartis).

<span class="mw-page-title-main">Auranofin</span> Chemical compound

Auranofin is a gold salt classified by the World Health Organization as an antirheumatic agent. It has the brand name Ridaura.

Antiprotozoal agents is a class of pharmaceuticals used in treatment of protozoan infection.

<span class="mw-page-title-main">Miltefosine</span> Phospholipid drug

Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as Naegleria fowleri and Balamuthia mandrillaris. This includes the three forms of leishmaniasis: cutaneous, visceral and mucosal. It may be used with liposomal amphotericin B or paromomycin. It is taken by mouth.

<span class="mw-page-title-main">Nitazoxanide</span> Chemical compound

Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.

<span class="mw-page-title-main">Diloxanide</span> Medication for amoebic gut infections

Diloxanide is a medication used to treat amoeba infections. In places where infections are not common, it is a second line treatment after paromomycin when a person has no symptoms. For people who are symptomatic, it is used after treatment with metronidazole or tinidazole. It is taken by mouth.

<span class="mw-page-title-main">Protozoan infection</span> Parasitic disease caused by a protozoan

Protozoan infections are parasitic diseases caused by organisms formerly classified in the kingdom Protozoa. They are usually contracted by either an insect vector or by contact with an infected substance or surface and include organisms that are now classified in the supergroups Excavata, Amoebozoa, SAR, and Archaeplastida.

An amebicide is an agent that is destructive to amoeba, especially parasitic amoeba that cause amoebiasis.

<span class="mw-page-title-main">Amoebiasis</span> Human disease caused by amoeba protists

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 ulcerations, abdominal pain, diarrhea, or bloody diarrhea. Complications can include inflammation and ulceration of the colon with tissue death or perforation, which may result in peritonitis. Anemia may develop due to prolonged gastric bleeding.

<span class="mw-page-title-main">Amoebic liver abscess</span> Medical condition

A amoebic liver abscess is a type of liver abscess caused by amebiasis. It is the involvement of liver tissue by trophozoites of the organism Entamoeba histolytica and of its abscess due to necrosis.

<span class="mw-page-title-main">Amoebic brain abscess</span> Medical condition

Amoebic brain abscess is an affliction caused by the anaerobic parasitic protist Entamoeba histolytica. It is extremely rare; the first case being reported in 1849. Brain abscesses resulting from Entamoeba histolytica are difficult to diagnose and very few case reports suggest complete recovery even after the administration of appropriate treatment regimen.

Cutaneous amoebiasis, refers to a form of amoebiasis that presents primarily in the skin. It can be caused by Acanthamoeba or Entamoeba histolytica. When associated with Acanthamoeba, it is also known as "cutaneous acanthamoebiasis". Balamuthia mandrillaris can also cause cutaneous amoebiasis, but can prove fatal if the amoeba enters the bloodstream It is characterized by ulcers. Diagnosis of amebiasis cutis calls for high degree of clinical suspicion. This needs to be backed with demonstration of trophozoites from lesions. Unless an early diagnosis can be made such patients can develop significant morbidity.

<span class="mw-page-title-main">Glaucarubin</span> Chemical compound

Glaucarubin is a quassinoid derived from the tropical shrub, Simarouba glauca. It is used as an antiamoebic agent.

Entamoeba moshkovskii is part of the genus Entamoeba. It is found in areas with polluted water sources, and is prevalent in places such as Malaysia, India, and Bangladesh, but more recently has made its way to Turkey, Australia, and North America. This amoeba is said to rarely infect humans, but recently this has changed. It is in question as to whether it is pathogenic or not. Despite some sources stating this is a free living amoeba, various studies worldwide have shown it contains the ability to infect humans, with some cases of pathogenic potential being reported. Some of the symptoms that often occur are diarrhea, weight loss, bloody stool, and abdominal pain. The first known human infection also known as the "Laredo strain" of Entamoebic mushkovskii was in Laredo, Texas in 1991, although it was first described by a man named Tshalaia in 1941 in Moscow, Russia. It is known to affect people of all ages and genders.

Entamoeba invadens is an amoebozoa parasite of reptiles, within the genus Entamoeba. It is closely related to the human parasite Entamoeba histolytica, causing similar invasive disease in reptiles, in addition to a similar morphology and lifecycle.

References

  1. Abdi, Y. A. (1995). Handbook of drugs for tropical parasitic infections. Washington, DC: Taylor & Francis. p. 47. ISBN   0-7484-0168-7.
  2. "Center for Disease Control NCID Formulary" . Retrieved 2007-09-09.
  3. Magaña-García M, Arista-Viveros A (1993). "Cutaneous amebiasis in children". Pediatric Dermatology. 10 (4): 352–5. doi:10.1111/j.1525-1470.1993.tb00397.x. PMID   8302738. S2CID   41438097.
  4. Chong-Hwee, Chun; Pil-Won, Park; O-Jeung, Lee; Soo-Young, Pak. "Amoebic Comparative Double Blind Trials of Tiberal Compared with Metronidazole and Oral Dehydroemetine in Oligosymptomatie Amoebiasis". Korean Medical Database. The Korean Society of Infectious Diseases & Korean Society for Chemotherapy. 6 (1): 97–104. Retrieved November 9, 2015.
  5. Peters M, Dietrich M, Bienzle U, Kern P, Mannweiler E (1979). "Amoebic liver abscess: a retrospective clinical evaluation of twenty-seven cases". Tropenmedizin und Parasitologie. 30 (4): 409–16. PMID   538815.
  6. Chintana T, Sucharit P, Mahakittikun V, Siripanth C, Suphadtanaphongs W (1986). "In vitro studies on the sensitivity of local Entamoeba histolytica to anti-amoebic drugs". Southeast Asian J. Trop. Med. Public Health. 17 (4): 591–4. PMID   2883732.
  7. Panwar P, Burusco KK, Abubaker M, Matthews H, Gutnov A, Fernandez-Alvaro E, Bryce RA, Wilkinson J, Nirmalan N (2020). "Lead Optimization of Dehydroemetine for Repositioned Use in Malaria". Antimicrobial Agents and Chemotherapy. 64 (4). e01444-19. doi: 10.1128/AAC.01444-19 . PMC   7179302 . PMID   31964796.
  8. Hernandez-Perez E (1980). "Dehydroemetine therapy for herpes zoster. A comparison with corticosteroids". Cutis; Cutaneous Medicine for the Practitioner. 25 (4): 424–6. PMID   6102504.
  9. Al-Khateeb GH, Al-Jeboori TI, Al-Janabi KA (1977). "In vitro efficacy of some drugs on promastigotes of Leishmania donovani". Chemotherapy. 23 (4): 267–75. doi:10.1159/000221994. PMID   16732.