Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects
Abstract
:1. Introduction
2. History
3. Structure and Chemical Properties
4. Avermectin Biosynthesis
5. Avermectin Derivatives, Formulations, Therapeutic and Toxic Dosages, and Mechanism of Action
5.1. Avermectin Derivatives and Its Formulations
5.1.1. Ivermectin
5.1.2. Moxidectin
5.1.3. Selamectin
5.1.4. Abamectin (Avermectin B1)
5.1.5. Milbemycin
5.1.6. Doramectin, Eprinomectin, and Nemadectin
5.2. Dosing
5.2.1. Mechanism of Action
5.2.2. Mode of Action of Milbemycins
5.2.3. Mode of Action of Spinosyns
6. Pharmacological Effects of Ivermectin
6.1. Human Uses of Ivermectin
6.2. Efficacy against Plant Parasitic Nematodes
6.3. Antibacterial Action
6.4. Endectocides for Malaria Control
6.5. Anti-Inflammatory Effect of Avermectin
6.6. Anticancer
6.7. Metabolic Effect of IVM
6.8. Anti-Alcohol Therapies
6.9. Antitumor Effect of Avermectins
6.10. Antiviral Effects
6.11. Ivermectin and Coronavirus
6.12. Metabolic Effects of Ivermectin
7. Pharmacokinetics
8. Environmental Effects of the Usage of Avermectins in Livestock
9. Clinical Trials of Avermectins
10. Toxicity and Side Effects
10.1. Neurotoxicology of Ivermectin
10.2. Toxic Effect of Ivermectin
11. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | Chemical Structures | Synonyms | IUPAC Name | Molecular Formula | Ref. |
---|---|---|---|---|---|
Ivermectin | Eqvalan Ivermectin Ivomec Mectizan MK 933 Stromectol | 1R,4S,5′S,6R,6′R,8R,10E,12S,13S,14E,16E,20R,21R,24S)-6′-[(2S)-butan-2-yl]-21,24-dihydroxy-12-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-5′,11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2′-oxane]-2-one | C48H74O14 | [39] | |
Selamectin | Selamectin UNII- 220119-17-5 A2669OWX9N UK-124,114 | ((2aE,4E,8E,20Z)-(5′S,6S,6′S,7S,11R,13R,15S,17aR,20aR,20bS)-6′-cyclohexyl-3′,4′,5′,6,6′,7,10,11,14,15,17a,20,20a,20b-tetradecahydro-20b-hydroxy-20-(hydroxyimino)-5′,6,8,19-tetramethyl-17-oxospiro[11,15-methano-2H,13H,17H-furo[4,3,2-pq][2,6]benzodioxacyclooctadecin-13,2′-[2H]pyran]-7-yl 2,6-dideoxy-3-O-methyl-α-L-arabino-hexopyranoside | C43H63NO11 | ||
Moxidectin | ProHeart 6 CL301423 Cydectin | 1R,4S,5′S,6R,6′S,8R,10E,12S,13S,14E,16E,20R,21Z,24S)-6′-cyclohexyl-24-hydroxy-21-hydroxyimino-12-[(2R,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-5′,11,13,22-tetramethylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2′-oxane]-2-one | C37H53NO8 | ||
Doramectin | DECTOMAX UK-67,994 | (1′R,2R,3S,4′S,6S,8′R,10′E,12′S,13′S,14′E,16′E,20′R,21′R,24′S)-2-cyclohexyl-21′,24′-dihydroxy-12′-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-3,11′,13′,22′-tetramethylspiro[2,3-dihydropyran-6,6′-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-2′-one | C50H74O14 | ||
Eprinomectin | Avermectin B1, 4″-(acetylamino)-4″-deoxy-, (4″R)- Eprinex Eprinomectin [USAN:USP:INN] MK 397 ZINC306122586 | (N-[(2S,3R,4S,6S)-6-[(2S,3S,4S,6R)-6-[(1′R,2R,3S,4′S,6S,8′R,10′E,12′S,13′S,14′E,16′E,20′R,21′R,24′S)-21′,24′-dihydroxy-3,11′,13′,22′-tetramethyl-2′-oxo-2-propan-2-ylspiro[2,3-dihydropyran-6,6′-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-12′-yl]oxy-4-methoxy-2-methyloxan-3-yl]oxy-4-methoxy-2-methyloxan-3-yl]acetamido | C49H73NO14 | ||
Nemadectin | Nemadectin UNII-1Y8VJ1G3TY 1Y8VJ1G3TY 102130-84-7 Nemadectina | ((1R,4S,4′S,5′S,6R,6′S,8R,10E,13R,14E,16E,20R,21R,24S)-4′,21,24-trihydroxy-5′,11,13,22-tetramethyl-6′-[(E)-4-methylpent-2-en-2-yl]spiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2′-oxane]-2-one | C36H52O8 | ||
Milbemycin | Milbemycin D Antibiotic B 41D Milbemycin B 41D UNII-04S0E2XJQI | ((1R,4S,5′S,6R,6′R,8R,10E,13R,14E,16E,20R,21R,24S)-21,24-dihydroxy-5′,11,13,22-tetramethyl-6′-propan-2-ylspiro[3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene-6,2′-oxane]-2-one | C33H48O7 | ||
Abamectin | Abamectinum Agrimek Vertimec Affirm Avomec | ((1′R,2R,3S,4′S,6S,8′R,10′E,12′S,13′S,14′E,16′E,20′R,21′R,24′S)-2-butan-2-yl-21′,24′-dihydroxy-12′-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-3,11′,13′,22′-tetramethylspiro[2,3-dihydropyran-6,6′-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-2′-one | C95H142O28 |
Uses | Ref. |
---|---|
Onchocerca volvulus | [73] |
Strongyloidiasis | [74,75] |
Scabies | [78] |
Papulopustular rosacea (PPR) | [79] |
Pediculosis | [74,76] |
Gnathostomiasis | |
Myiasis | |
Leishmaniasis | |
Trichuris | |
Ascaris |
Activity | Compound | Organism Active Against | Ref. |
---|---|---|---|
Nematocidal | Abamectin | Hoplolaimus galeatus and Tylenchorynchus dubius, E. vermiculata | [88,89] |
Antibacterial | Ivermectin Selamectin Doramectin Moxidectin | Mycobacterium bovis and M. tuberculosis | [93,96,97] |
Anti-plasmodium | Ivermectin | P. falciparum | [104] |
Anti-inflammatory | Ivermectin | Skin inflammation | [111] |
Anticancer | Ivermectin | Lung cancer and colon cancer | [118] |
Antiviral | Ivermectin | Dengue virus and yellow fever virus | [28] |
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El-Saber Batiha, G.; Alqahtani, A.; Ilesanmi, O.B.; Saati, A.A.; El-Mleeh, A.; Hetta, H.F.; Magdy Beshbishy, A. Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects. Pharmaceuticals 2020, 13, 196. https://doi.org/10.3390/ph13080196
El-Saber Batiha G, Alqahtani A, Ilesanmi OB, Saati AA, El-Mleeh A, Hetta HF, Magdy Beshbishy A. Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects. Pharmaceuticals. 2020; 13(8):196. https://doi.org/10.3390/ph13080196
Chicago/Turabian StyleEl-Saber Batiha, Gaber, Ali Alqahtani, Omotayo B. Ilesanmi, Abdullah A. Saati, Amany El-Mleeh, Helal F. Hetta, and Amany Magdy Beshbishy. 2020. "Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects" Pharmaceuticals 13, no. 8: 196. https://doi.org/10.3390/ph13080196
APA StyleEl-Saber Batiha, G., Alqahtani, A., Ilesanmi, O. B., Saati, A. A., El-Mleeh, A., Hetta, H. F., & Magdy Beshbishy, A. (2020). Avermectin Derivatives, Pharmacokinetics, Therapeutic and Toxic Dosages, Mechanism of Action, and Their Biological Effects. Pharmaceuticals, 13(8), 196. https://doi.org/10.3390/ph13080196