pyrantel and Paralysis

Levamisole is an anthelmintic drug that acts by activating nicotinic acetylcholine receptors at the nematode neuromuscular junction and causing paralysis. We measured the in vitro effects of levamisole on the motility of Brugia malayi microfilariae; after 2 h incubation the apparent IC50 was 2.68 mM. Lower drug concentrations, such as 1 mM, caused an immediate total paralysis that lasted for up to 1 h, but was completely reversed by 2 h of incubation. The 'recovered' parasites were still completely susceptible to application of a second nicotinic agonist, pyrantel.

Topics: Animals; Antinematodal Agents; Brugia malayi; Dose-Response Relationship, Drug; Levamisole; Microfilariae; Paralysis; Pyrantel

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.

Topics: Angiostrongylus cantonensis; Animals; Antinematodal Agents; Bicuculline; Female; Guanidine; Guanidines; Hemicholinium 3; In Vitro Techniques; Macrolides; Muscle Contraction; Muscle, Skeletal; Paralysis; Phentolamine; Physostigmine; Picrotoxin; Pyrantel; Rats; Rats, Wistar; Strychnine; Sympatholytics

Topics: Animals; Anthelmintics; Bephenium Compounds; Binding Sites; Ganglia; Levamisole; Membrane Potentials; Movement; Muscle Contraction; Nematoda; Paralysis; Pyrantel; Pyridines