Stereochemical preferences for curarimimetic neuromuscular junction blockade I: enantiomeric monoquaternary amines as probes.
Seven pairs of monoquaternary enantiomeric neuromuscular junction blocking agents were prepared in which the carbon asymmetry is adjacent to the quaternized nitrogen moiety. The tertiary amines from which the blocking species were obtained are carnegine, laudanosine, N-methylpavine, corydine, isocorydine, glaucine, and boldine. Curarimimetic potencies, obtained with an in vivo cat tongue-hypoglossal nerve preparation, were obtained for the enantiomeric methiodides of each of these amines. Possible contributions to activity be preferential binding to blood components or by selective inhibition of acetylcholinesterase also were studied. The combined studies indicate that there is a modest preference by the neuromuscular junction of the cat for monoquaternary blockers with the (s)-confirguation.
D000109:Acetylcholine / Q000097:blood; D000588:Amines / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D001798:Blood Proteins / Q000378:metabolism; D002415:Cats; D055598:Chemical Phenomena; D002621:Chemistry; D002800:Cholinesterase Inhibitors; D004305:Dose-Response Relationship, Drug; D004491:Edrophonium / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D007002:Hypoglossal Nerve / Q000187:drug effects; D007700:Kinetics; D008297:Male; D008968:Molecular Conformation; D009467:Neuromuscular Depolarizing Agents / Q000032:analysis; D003473:Neuromuscular Nondepolarizing Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D013056:Spectrophotometry, Ultraviolet; D014059:Tongue / Q000187:drug effects; D014403:Tubocurarine / Q000494:pharmacology
D000588:Amines; D001798:Blood Proteins; D002800:Cholinesterase Inhibitors; D009467:Neuromuscular Depolarizing Agents; D003473:Neuromuscular Nondepolarizing Agents; D004491:Edrophonium; D000109:Acetylcholine; D014403:Tubocurarine