pralidoxime and acetaldehyde-oxime

O-Substituted aldoximes of the cholinesterase reactivator pralidoxime (O-methyl 1, O-benzyl 2, O-propynyl 3 and O-butynyl 4 derivatives) were synthesized and found to exhibit strong binding affinities for muscarinic receptors in rat brain, heart and submandibulary glands. The aldoximes were noncompetitive antagonists of acetylcholine-induced contraction of the guinea pig ileum. A good correlation was observed between binding affinity and pK(B). Weak anticholinesterase activities were observed for these compounds. When given intracerebroventricularly into conscious rats before soman administration (0.9 LD(50), subcutaneously), the aldoximes, like atropine but not pralidoxime, protected against respiratory depression (3,4) and bradycardia (2). No protection against soman-induced pressor effects was noted. The protective effects of these aldoximes may be the outcome of compensatory mechanisms, of which the cholinergic receptor agonist and antagonist properties of these compounds may be important.

Topics: Acetylcholinesterase; Animals; Atropine; Binding, Competitive; Blood Pressure; Brain; Carbachol; Cholinergic Agonists; Cholinesterase Inhibitors; Cholinesterase Reactivators; Dose-Response Relationship, Drug; Female; Guinea Pigs; Heart Rate; Ileum; In Vitro Techniques; Male; Muscarinic Antagonists; Muscle Contraction; Myocardium; Oximes; Pralidoxime Compounds; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Respiration; Soman; Structure-Activity Relationship; Submandibular Gland

Topics: Humans; Hydrocarbons, Iodinated; Hydroxylamines; Oximes; Parathion; Pralidoxime Compounds; Pyridines

Topics: Animals; Isoflurophate; Mice; Oximes; Parathion; Phosphates; Pralidoxime Compounds; Pyridines