Actions of potent cholinergic anthelmintics (morantel, pyrantel and levamisole) on an identified insect neurone reveal pharmacological differences between nematode and insect acetylcholine receptors.
Intracellular recording and current-clamp techniques were used to investigate the cholinergic activity of the anthelmintics, morantel, pyrantel and levamisole, applied to the fast coxal depressor motorneurone (Df) of the cockroach Periplaneta americana. Application of these agents and acetylcholine to the bath resulted in dose-dependent changes in conductance and corresponding depolarization of the neuronal membrane. Relative potencies of the drugs were determined from dose-response relationships and the rank order of effectiveness was as follows: carbachol much greater than levamisole greater than pyrantel greater than morantel. Evidence that these drugs were acting at the same site of action was obtained with the antagonist, mecamylamine, which abolished the responses to all these agents. It is concluded that the weak insecticidal action of these potent anthelmintics may result in part from their weak cholinergic agonist action on insect neurones, which contrasts with their potent agonist actions on acetylcholine receptors of helminth nerve and muscle tissues. The striking differences in potency on different invertebrate tissues appears to reflect differences in the properties of acetylcholine receptors between insects and nematodes. Further characterization of neurotransmitter receptors in invertebrates is needed in order to facilitate the rational design of broad-spectrum antiparasitic agents with low toxicity in mammals.
Pinnock
R D
RD
Department of Zoology, University of Cambridge, U.K.
Sattelle
D B
DB
Gration
K A
KA
Harrow
I D
ID
D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D003058:Cockroaches / Q000502:physiology*; D004594:Electrophysiology; D007478:Iontophoresis; D007978:Levamisole / Q000494:pharmacology*; D008464:Mecamylamine / Q000494:pharmacology; D009015:Morantel / Q000494:pharmacology*; D009046:Motor Neurons / Q000187:drug effects; D009348:Nematoda / Q000502:physiology*; D009474:Neurons / Q000187:drug effects*; D010277:Parasympathomimetics / Q000494:pharmacology*; D011715:Pyrantel / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects*
D000871:Anthelmintics; D010277:Parasympathomimetics; D011743:Pyrimidines; D011950:Receptors, Cholinergic; D007978:Levamisole; D011715:Pyrantel; D008464:Mecamylamine; D009015:Morantel