Electron microscopic studies on the effects of CGP 6140 and CGP 20376 on microfilariae and third stage larvae of Onchocerca volvulus.

Electron microscopic examination was used to assess the effects of CGP 6140 (proposed generic name: amocarcine) and CGP 20376 (proposed generic name: metobethiamide) on the fine structure of microfilariae and third stage larvae of Onchocerca volvulus after in vitro exposure to different concentrations of these compounds. The range of concentrations was selected according to the expected plasma levels that may be reached with these drugs. The microfilariae showed distinct effects on the muscle cells as myelin figures, vacuolisation and disintegration of the cytoplasm after both compounds. The third stage larvae showed the same effects on the muscle cells including changes in the mitochondria and the hypodermal tissue. In addition, the glandular esophagus demonstrated degenerative alterations of the cytoplasm and loosening of the cuticular lining after exposure to CGP 6140. CGP 20376 led to severe damage of the fibres of the nerve ring. No degenerative changes of the microtubuli were observed. Comparison of the morphological effects observed by electron microscopy with the reduction rates of motility and moulting recorded in the in vitro tests showed good correlation between these different parameters. The observed effect on the fine structure was the most sensitive parameter.