Biomaterial Database

Diethylcarbamazine increases activation of voltage-activated potassium (SLO-1) currents in Ascaris suum and potentiates effects of emodepside. 2014

Samuel K Buxton, and Alan P Robertson, and Richard J Martin

Department of Biomedical Sciences, Iowa State University, Ames, Iowa, United States of America.

Diethylcarbamazine is a drug that is used for the treatment of filariasis in humans and animals; it also has effects on intestinal nematodes, but its mechanism of action remains unclear. Emodepside is a resistance-busting anthelmintic approved for treating intestinal parasitic nematodes in animals. The novel mode of action and resistance-breaking properties of emodepside has led to its use against intestinal nematodes of animals, and as a candidate drug for treating filarial parasites. We have previously demonstrated effects of emodepside on SLO-1 K+-like currents in Ascaris suum. Here, we demonstrate that diethylcarbamazine, which has been proposed to work through host mediated effects, has direct effects on a nematode parasite, Ascaris suum. It increases activation of SLO-1 K+ currents and potentiates effects of emodepside. Our results suggest consideration of the combination of emodepside and diethylcarbamazine for therapy, which is predicted to be synergistic. The mode of action of diethylcarbamazine may involve effects on parasite signaling pathways (including nitric oxide) as well as effects mediated by host inflammatory mediators.

UI	MeSH Term	Description	Entries
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004049	Diethylcarbamazine	An anthelmintic used primarily as the citrate in the treatment of filariasis, particularly infestations with Wucheria bancrofti or Loa loa.	Carbamazine,Diethylcarbamazine Citrate,Diethylcarbamazine Citrate (1:1),Diethylcarbamazine Citrate (1:2),Diethylcarbamazine L-Tartrate (1:1),Diethylcarbamazine Maleate,Diethylcarbamazine Monohydrochloride,Diethylcarbamazine Phosphate (1:1),Hetrazan,Loxuran,Notezine,Citrate, Diethylcarbamazine,Maleate, Diethylcarbamazine,Monohydrochloride, Diethylcarbamazine
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005369	Filaricides	Pharmacological agents destructive to nematodes in the superfamily Filarioidea.
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000871	Anthelmintics	Agents that kill parasitic worms. They are used therapeutically in the treatment of HELMINTHIASIS in man and animal.	Anthelmintic,Antihelmintic,Vermifuge,Vermifuges,Antihelmintics
D017165	Ascaris suum	A species of parasitic nematode usually found in domestic pigs and a few other animals. Human infection can also occur, presumably as result of handling pig manure, and can lead to intestinal obstruction.	Ascaris suums,suum, Ascaris
D047630	Depsipeptides	Compounds consisting of chains of AMINO ACIDS alternating with CARBOXYLIC ACIDS via ester and amide linkages. They are commonly cyclized.	Cyclic Depsipeptide,Cyclodepsipeptide,Depsipeptide,Peptolide,Peptolides,Cryptophycins,Cyclodepsipeptides,Depsipeptides, Cyclic,Cyclic Depsipeptides,Depsipeptide, Cyclic