Anionic cyclophanes as potential reversal agents of muscle relaxants by chemical chelation.
A series of carboxyl-containing cyclophanes have been designed and synthesised as chemical chelators (or host molecules) of cationic muscle relaxant drugs (or guest molecules). Three of these cyclophane derivatives, 1-3, have been shown by NMR to form 1:1 complexes with the muscle relaxants pancuronium, and gallamine, in D(2)O, with association constants up to 10(4) M(-1). When tested in an in vitro chick biventer muscle preparation, the cyclophanes reversed the neuromuscular block induced by pancuronium and gallamine, with having the most effective reversal against pancuronium (EC(50) 40 microM.
Cameron
Kenneth S
KS
Department of Analytical Chemistry, Organon Laboratories Ltd., Newhouse, Lanarkshire ML1 5SH, Scotland, UK.
Fielding
Lee
L
Mason
Rona
R
Muir
Alan W
AW
Rees
David C
DC
Thorn
Simon
S
Zhang
Ming Qiang
MQ
D000818:Animals; D000838:Anions / Q000737:chemistry; D002614:Chelating Agents / Q000494:pharmacology*; D002645:Chickens; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005703:Gallamine Triethiodide / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009465:Neuromuscular Agents / Q000494:pharmacology*; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D010197:Pancuronium / Q000494:pharmacology
D000838:Anions; D002614:Chelating Agents; D004988:Ethers, Cyclic; D009465:Neuromuscular Agents; D003473:Neuromuscular Nondepolarizing Agents; D010197:Pancuronium; D005703:Gallamine Triethiodide