In vitro effects of VD-99-11 on Angiostrongylus cantonensis and isolated frog rectus.
In vitro effects of VD-99-11 were examined using adult Angiostrongylus cantonensis and isolated frog rectus. In A. cantonensis, paralysis was elicited by VD-99-11 at 10(-9)-10(-6) g/ml. The paralysis caused by VD-99-11 (10(-8) g/ml) was antagonized by picrotoxin or bicuculline but not by phentolamine. A relationship between VD-99-11 and gabergic antagonists was observed in worm preparations contracted by eserine or pyrantel: VD-99-11 at higher concentrations (3x10(-6) g/ml) caused a marked contraction. In worm preparations contracted with eserine or pyrantel, the only additional contraction induced by VD-99-11 (5x10(-6) g/ml) was antagonized by strychnine. In experiments on the guanidine (2.5x10(-3) M)-induced twitch responses in isolated frog rectus, marked stimulation was caused by VD-99-11 (3-5x10(-6) g/ml). The stimulated responses induced by VD-99-11 were antagonized by tetrodotoxin, D-tubocurarine, strychnine, and hemicholinium-3, respectively. These results suggest that VD-99-11 seems superior to milbemycin D, milbemycin oxime, and ivermectin in some aspects, such as in vitro potency, though this new substance is similar to these drugs in having two different actions on the gabergic mechanism at lower concentrations and on the cholinergic mechanism at higher concentrations.
D017185:Angiostrongylus cantonensis / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D005260:Female; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology; D006426:Hemicholinium 3 / Q000494:pharmacology; D066298:In Vitro Techniques; D018942:Macrolides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D010243:Paralysis; D010646:Phentolamine / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011715:Pyrantel / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013331:Strychnine / Q000494:pharmacology; D013565:Sympatholytics / Q000494:pharmacology
D000969:Antinematodal Agents; D001640:Bicuculline; D019791:Guanidine; D006146:Guanidines; D006426:Hemicholinium 3; D018942:Macrolides; D010646:Phentolamine; D010830:Physostigmine; D010852:Picrotoxin; D011715:Pyrantel; D013331:Strychnine; D013565:Sympatholytics; C096649:VD 99-11