A comparison of the response of Dipetalonema viteae and Brugia pahangi adult worms to antifilarial agents in vitro.
The drug response of Dipetalonema viteae and B. pahangi under various culture conditions have been evaluated. B. pahangi female worms proved to be more susceptible to CGP 6140 (4-nitro-4'-(N-methyl)piperazinyl thiocarbonylido-diphenylamine), CGP 20376 (N-(2-tert-butyl-5-methoxy-benzothiazol-6-yl)dithiocarbonic acid 5-(1-carboxyethyl)-ether) and amoscanate when glucose availability was restricted. This increased potency may be related to effects on glycogen metabolism by CGP 20376 and amoscanate. Using the parameters of parasite motility, survival, glucose consumption and microfilarial output, Eagles Minimum Essential Medium supplemented with 10% inactivated foetal calf serum plus either a 95% air:5% CO2 or a 95% N2:5% CO2 gas phase was shown to be highly suitable for short term maintenance (5 days). Examination of 12 drugs selected on their in vivo activity against B. pahangi and D. viteae demonstrated little difference between the drug susceptibilities of male and female worms. However, there were intrinsic differences between worm species. The relationship between these disparate susceptibilities and the reported in vivo efficacies of these drugs and the importance of selecting appropriate conditions for in vitro drug assays are discussed. Ivermectin at 10(-5) M caused a rapid flaccid paralysis and a complete suppression of microfilarial output by D. viteae. Despite continued paralysis of the worms they continued to utilise as much glucose as untreated worms over a 4 day period.
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D002009:Brugia / Q000187:drug effects* / Q000378:metabolism; D004153:Dipetalonema / Q000187:drug effects* / Q000378:metabolism; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005369:Filaricides / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D017879:Isothiocyanates; D007559:Ivermectin / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013861:Thiocyanates / Q000494:pharmacology
D000871:Anthelmintics; D005369:Filaricides; D017879:Isothiocyanates; D010879:Piperazines; D013844:Thiazoles; D013861:Thiocyanates; D007559:Ivermectin; C051745:CGP 20376; C051744:amocarzine; D004159:Diphenylamine; D005947:Glucose; C012391:amoscanate