1. Muscle type of nicotinic acetylcholine receptor (nAChR) in mammals, and nematodes, the similarities and differences as a key for the selective toxicity of anthelmintic drugs

The most commonly used antinematodal drugs in human and veterinary medicine are cholinergic agonists: imidazothiazole (praziquantel) tetrahydropyrimidines (pyrantel, morantel, and oxantel), quaternary/tertiary amines (bephenium and tribendimidine), pyridines (methyridine), and the amino-acetonitrile derivatives (AADs). These antiparasitic drugs produce spastic paralysis of the nematodes by selective gating acetylcholine receptor ion-channels in the nerve and muscle cells. Exceptions are AADs, because their mechanism of action on the nAChR is not fully understood. However, the key to their effective and safe use is selective toxicity, i.e. the difference between the nicotinic acetylcholine receptors (nAChRs) in the nematodes (parasite) and Correspondence/Reprint request: Prof. dr. Saša M. Trailović, Professor of Pharmacology and Toxicology Faculty of Veterinary Medicine, University of Belgrade, Belgrade, Serbia. E-mail: [email protected] Saša M. Trailović et al. 2 nicotinic receptors at the motor end-plate in mammals (host). None of these drugs is able to pass the blood brain barrier in a respectable amount, therefore their interaction with host central nicotinic receptors is almost impossible. On the other hand, the effects of antinematodal drugs on nicotinic receptors in autonomic ganglia are rarely mentioned and not proven in clinical practice. This is supported by data that almost all the described side effects may be related to the interaction with peripheral nicotinic receptors in the host (muscle tremors, impaired breathing the diaphragm function, disturbance of cardiac function). In the human medicine, nAChRs have been implicated in several neuromuscular and neurological disorders, as a consequence of that, they are become interesting drugable target for discovery of new drugs. The roles of these receptors in myasthenia gravis, Alzheimer‟s and Parkinson‟s diseases, schizophrenia, as well as in the cessation of smoking are the subject of many studies in different fields of medicine. There are many reasons why we are particularly interested to analyze, investigate, and compare the characteristics of the mammalian muscle-type, and nematode nicotinic acetylcholine receptors, but most important is to realize the possibilities for improving the treatment of parasitic infections, as well as better understanding physiological disorders, related to altered function of cholinergic system in mammals.