Neuromuscular blocking agents and axial teratogenesis in the avian embryo. Can axial morphogenetic disorders by explained by pharmacological action upon muscle tissue?
A comparative qualitative and quantitative study of the embryotoxic and teratogenic activities of various chemical agents known to have neuromuscular blocking properties was done on the quail embryo. Intrinsic embryotoxic activity and teratogenicity were evaluated for each agent, and the qualitative nature of the teratogenic effects was correlated with the pharmacologic properties of the different effectors. Gross malformations (contorted posture) were found only with agents which directly (cholinergic agonists) or indirectly (cholinesterase inhibitors) favor muscle membrane depolarization, suggesting that such malformations may be due to muscle contraction following depolarization. All of the agents studied produced variable degrees of vertebral fusion, apparently due to paralysis resulting either from sustained depolarization (cholinesterase inhibitors and cholinergic agonists) or directly from cholinergic blockade (cholinergic antagonists and neurotoxins).
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003370:Coturnix / Q000196:embryology*; D003650:Decamethonium Compounds / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D009132:Muscles / Q000002:abnormalities; D009388:Neostigmine / Q000494:pharmacology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010278:Parathion / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011784:Quail / Q000196:embryology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D013723:Teratogens; D014403:Tubocurarine / Q000494:pharmacology
D002038:Bungarotoxins; D003650:Decamethonium Compounds; D006584:Hexamethonium Compounds; D009466:Neuromuscular Blocking Agents; D009943:Organophosphorus Compounds; D000644:Quaternary Ammonium Compounds; D013723:Teratogens; D009388:Neostigmine; D010278:Parathion; D009538:Nicotine; D002217:Carbachol; D010830:Physostigmine; C000944:dicrotophos; C100193:demecarium; D005703:Gallamine Triethiodide; D014403:Tubocurarine