Campbell WC et al. (1996) J Parasitol "Effect of ivermectin on Caenorhabditis elegans larvae previously exposed to alcoholic immobilization."

Smith H, Campbell WC

[J Parasitol, 1996]

First-stage larvae of Caenorhabditis elegans were immersed in 0.15% 1-phenoxy-2-propanol to induce temporary paralysis, including the suppression of pharyngeal pumping. Subsequent addition of ivermectin (to give 50 micrograms/ml) induced coiling and prolonged immobilization of such larvae, as also of control larvae (previously immersed only in water). The results suggest that ingestion of drug by means of pharyngeal pumping is not a prerequisite for the uptake of ivermectin at levels sufficient for antinematodal action.

Fasiuddin A et al. (2000) J Parasitol "Haemonchus contortus (Nematoda: Trichostrongylidae) is much more sensitive than Caenorhabditis elegans (Nematoda: Rhabditidae) to the ovicidal action of thiabendazole."

Campbell WC, Fasiuddin A

[J Parasitol, 2000]

When eggs of the trichostrongylid nematode Haemonchus contortus were exposed to thiabendazole, the concentration required to prevent hatching in 90% of the eggs (MIC90) was found to be 0.1 mu g/ ml (using 1% dimethylsulfoxide [DMSO] as solvent). In contrast, eggs of the free-living rhabditid nematode Caenorhabditis elegans hatched at normal rates at a concentration 200 times higher, i.e., 20 mu g/ml, and showed only a partial inhibitory effect at a concentration 1,200 times higher, i.e., 120 mu g/ml (in 3% DMSO). Because solubility limitations precluded the testing of higher concentrations of thiabendazole, a more soluble derivative, 5-([1-methylethoxyl carbonylamino)-2-(4-thiazloyl)-1H-benzimidazolyliminoacetic acid N,N-diethylethanamine salt, was rested against C. elegans eggs. The MIC90 was found to be 400 mu g/ml, and although the derivative was not tested against H. contortus eggs, this finding further suggests that C. elegans eggs have an exceptionally low degree of benzimidazole sensitivity.

Gabriel EM et al. (2003) Parasitol Res "Effect of ambient salinity on immobilization of Caenorhabditis elegans by nematocidal agents."

Gabriel EM, Campbell WC

[Parasitol Res, 2003]

The ability of three antinematodal agents to induce paralysis of Caenorhabditis elegans was examined in an aqueous medium with and without the addition of salts. The basic medium was deionized water supplemented, for control purposes, with the phosphate mixture used as a buffering agent in M9 solution. This medium was further supplemented with magnesium sulfate or sodium chloride, or both salts, at the concentrations used in M9. We report that the paralyzing property of ivermectin was enhanced by the presence of salt, while the efficacy of levamisole and chlorpromazine was reduced.

Patel MR et al. (1998) J Parasitol "Inhibitory effect of chlorpromazine on nematode eggs and larvae."

Patel MR, Campbell WC

[J Parasitol, 1998]

Chlorpromazine inhibited the hatching of eggs of the parasitic nematode Haemonchus contortus and the free-living nematode Caenorhabditis elegans. In both species, hatching occurred at a concentration of 100 microg/ml but was almost totally blocked at 400 microg/ml. In the case of C. elegans, the effect was shown to be reversible by removal of chlorpromazine after exposure of the eggs to the drug for 1 hr. Caenorhabditis elegans larvae that hatched in a chlorpromazine concentration of 100 microg/ml were killed, but those that hatched in a concentration of 6.25 microg/ml were not. Taken together with data published by others, these observations indicate that the first-stage larva of C. elegans is less sensitive to chlorpromazine than is the adult worm.

O'Lone RB et al. (2001) J Parasitol "Effect of refrigeration on the antinematodal efficacy of ivermectin."

O'Lone RB, Campbell WC

[J Parasitol, 2001]

Several observations have suggested that the anthelmintic ivermectin can affect nematodes by non-oral entry into the nematode body. To investigate this possibility further, we refrigerated Caenorhabditis elegans at 5 C to prevent its locomotion and to block the pharyngeal pumping that is so prominent a feature of its feeding. Worms were exposed to ivermectin (1-25 mug/ml) at that temperature for 1 hr,after which the medium was replaced by unmedicated medium at room temperature. After 1 hr at room temperature the worms were examined and counted to determine the degree to which irreversible immobilization had occurred. The drug was significantly less effective at 5 C than at room temperature. This reduction in potency could be attributed to a general cold-induced decline in the rate of the biochemical processes involved in drug action. Alternatively, the reduction could be attributed to the cold-induced blockade of pharyngeal pumping, which would suggest that the efficacy of ivermectin is partially the result of oral intake of drug. The fact that antinematodal efficacy was not entirely abrogated and reached a significant level despite blockade of pharyngeal pumping supports the former interpretation and is in accord with earlier indications that ivermectin can enter by non-oral routes. This conclusion is further supported by the observation that ivermectin is active against the nonfeeding third-stage larva of Haemonchus contortus.