Monepantel: From Discovery to Mode of Action

Parasitic Helminths: Targets, Screens, Drugs and Vaccines

Volumn , Issue , 2012, Pages 283-296

  Kaminsky, Ronald ^a   Rufener, Lucien ^a  

^a Institute for Biomedical Research   (China)

Author keywords

AAD 1566; Amino acetonitrile derivative; Anthelmintic; Discovery; Mode of action; Monepantel

Indexed keywords

EID: 84874250857     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527652969.ch17     Document Type: Chapter

References (29)

1. Ducray, P., Gauvry, N., Pautrat, F. et al. (2008) Discovery of amino-acetonitrile derivatives, a new class of synthetic anthelmintic compounds. Bioorg. Med. Chem. Lett., 18, 2935-2938.
2. van Wyk, J.A., Malan, F.S., and Randles, J.L., (1997) How long before resistance makes it impossible to control some field strains of Haemonchus contortus in South Africa with any of the modern anthelmintics? Vet. Parasitol., 70, 111-122.
3. Kaminsky, R., Gauvry, N., Schorderet, W.S. et al. (2008) Identification of the amino-acetonitrile derivative monepantel (AAD 1566) as anew anthelmintic drug development candidate. Parasitol. Res., 103, 931-939.
4. Bustamante, M., Steffan, P.E., Morlan, J.B. et al. (2009) The efficacy of monepantel, an amino-acetonitrile derivative, against gastrointestinal nematodes of sheep in three countries of southern Latin America. Parasitol. Res., 106, 139-144.
5. Hosking, B.C., Kaminsky, R., Sager, H. et al. (2010) A pooled analysis of the efficacy of monepantel, an aminoacetonitrile derivative against gastrointestinal nematodes of sheep. Parasitol. Res., 106, 529-532.
6. Kaminsky, R., Mosimann, D., Sager, H. et al. (2009) Determination of the effective dose rate of monepantel (AAD 1566) against adult gastro-intestinal nematodes in sheep. Int. J. Parasitol., 39, 443-446.
7. Sager, H., Hosking, B.C., Bapst, B. et al. (2009) Efficacy of the amino-acetonitrile derivative, monepantel, against experimental and natural adult stage gastro-intestinal nematodes infections in sheep. Vet. Parasitol., 159, 49-54.
8. Kaminsky, R., Bapst, B., Stein, P.A. et al. (2011) Differences in efficacy of monepantel, derquantel and abamectin against multi-resistant nematodes of sheep. Parasitol. Res., 109, 19-23.
9. Malikides, N., Spencer, K., Mahoney, R. et al. (2009) Safety of an amino-acetonitrile derivative (AAD), monepantel, in ewes and their offspring following repeated oral administration. NZ Vet. J., 57, 193-202.
10. Malikides, N., Helbig, R., Roth, D.R. et al. (2009) Safety of an amino-acetonitrile derivative (AAD), monepantel, in weaned lambs following repeated oral administration. NZ Vet. J., 57, 10-15.
11. Malikides, N., Helbig, R., Mahoney, R. et al. (2009) Reproductive safety of an amino-acetonitrile derivative (AAD), monepantel, in rams following repeated oral administration. NZ Vet. J., 57, 16-21.
12. Lewis, J.A., Wu, C.H., Levine, J.H. et al. (1980) Levamisole-resistant mutants of the nematode Caenorhabditis elegans appear to lack pharmacological acetylcholine receptors. Neuroscience, 5, 967-989.
13. Driscoll, M., Dean, E., Reilly, E. et al. (1989)Genetic and molecular analysis of a Caenorhabditis elegans beta-tubulin that conveys benzimidazole sensitivity. J. Cell Biol., 109, 2993-3003.
14. Nguyen, M., Alfonso, A., Johnson, C.D. et al. (1995)Caenorhabditis elegans mutants resistant to inhibitors of acetylcholinesterase. Genetics, 140, 527-535.
15. Dent, J.A., Davis, M.W., and Avery, L. (1997) avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans. EMBO J., 16, 5867-5879.
16. Dent, J.A., Smith, M.M., Vassilatis, D.K. et al. (2000) The genetics of ivermectin resistance in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA, 97, 2674-2679.
17. Wicks, S.R., Yeh, R.T., Gish, W.R. et al. (2001) Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map. Nat. Genet., 28, 160-164.
18. Jones, A.K. and Sattelle, D.B. (2004) Functional genomics of the nicotinic acetylcholine receptor gene family of the nematode, Caenorhabditis elegans. Bioessays, 26, 39-49.
19. Mongan, N.P., Baylis, H.A., Adcock, C. et al. (1998) An extensive and diverse gene family of nicotinic acetylcholine receptor alpha subunits in Caenorhabditis elegans. Receptors Channels, 6, 213-228.
20. Rufener, L., Keiser, J., Kaminsky, R. et al. (2010) Phylogenomics of ligand-gated ion channels predicts monepantel effect. PLoS Pathog., 6, e1001091.
21. Mongan, N.P., Jones, A.K., Smith, G.R. et al. (2002) Novel alpha7-like nicotinic acetylcholine receptor subunits in the nematode Caenorhabditis elegans. Protein Sci., 11, 1162-1171.
22. Brown, L.A., Jones, A.K., Buckingham, S.D. et al. (2006) Contributions from Caenorhabditis elegans functional genetics to antiparasitic drug target identification and validation:nicotinic acetylcholine receptors, a case study. Int. J. Parasitol., 36, 617-624.
23. Culetto, E., Baylis, H.A., Richmond, J.E. et al. (2004) The Caenorhabditis elegans unc-63 gene encodes a levamisolesensitive nicotinic acetylcholine receptor alpha subunit. J. Biol. Chem., 279, 42476-42483.
24. Fleming, J.T., Squire, M.D., Barnes, T.M. et al. (1997) Caenorhabditis elegans levamisole resistance genes lev-1, unc-29, and unc-38 encode functional nicotinic acetylcholine receptor subunits. J. Neurosci., 17, 5843-5857.
25. Kaminsky, R., Ducray, P., Jung, M. et al. (2008) A new class of anthelmintics effective against drug-resistant nematodes. Nature, 452, 176-180.
26. Rufener, L., Kaminsky, R., and Maser, P. (2009) In vitro selection of Haemonchus contortus for benzimidazole resistance reveals a mutation at amino acid 198 of beta-tubulin. Mol. Biochem. Parasitol., 168, 120-122.
27. Rufener, L., Baur, R., Kaminsky, R. et al. (2010) Monepantel allosterically activates DEG-3/DES-2 channels of the gastrointestinal nematode Haemonchus contortus. Mol. Pharmacol., 78, 895-902.
28. Karadzovska, D., Seewald, W., Browning, A. et al. (2009) Pharmacokinetics of monepantel and its sulfone metabolite, monepantel sulfone, after intravenous and oral administration in sheep. J. Vet. Pharmacol. Ther., 32, 359-367.
29. Rufener, L., Maser, P., Roditi, I. et al. (2009) Haemonchus contortus acetylcholine receptors of the DEG-3 subfamily and their role in sensitivity to monepantel. PLoS Pathog., 5, e1000380.