Asunto(s)
Androstanoles/química , Ciclodextrinas/química , Bloqueo Neuromuscular , Fármacos Neuromusculares no Despolarizantes/química , gamma-Ciclodextrinas , Androstanoles/farmacología , Animales , Cristalografía por Rayos X , Ciclodextrinas/farmacología , Diafragma/efectos de los fármacos , Diafragma/inervación , Técnicas In Vitro , Macaca mulatta , Ratones , Modelos Moleculares , Contracción Muscular/efectos de los fármacos , Fármacos Neuromusculares no Despolarizantes/farmacología , Rocuronio , SugammadexRESUMEN
A series benzylpiperidinium and benzylpyridinium quaternary salts have been synthesised and tested for inhibition of acetylcholinesterase and reversal of neuromuscular block induced by vecuronium. Several potent reversal agents have been identified and their haemodynamic effects measured.
Asunto(s)
Acetilcolinesterasa/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Indanos/farmacología , Fármacos Neuromusculares no Despolarizantes/antagonistas & inhibidores , Piperidinas/farmacología , Bromuro de Vecuronio/antagonistas & inhibidores , Inhibidores de la Colinesterasa/química , Donepezilo , Indanos/química , Piperidinas/químicaRESUMEN
A series of piperidinium and pyridinium agents containing a common structural fragment of 5,6-dimethoxybenzothiophene have been synthesised as water-soluble acetylcholinesterase inhibitors. Several compounds, for example 42 (AChE IC(50) 0.03 microM) have been found to reverse the neuromuscular blockade induced by vecuronium bromide in vitro and in vivo. Coupled with their high water solubility (up to 30-60 mg/mL), these compounds are potentially useful as intravenous reversal agents of neuromuscular blocking agents in surgical anaesthesia.
Asunto(s)
Acetilcolinesterasa/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Fármacos Neuromusculares no Despolarizantes/farmacología , Piperidinas/farmacología , Piridinas/farmacología , Bromuro de Vecuronio/antagonistas & inhibidores , Animales , Inhibidores de la Colinesterasa/química , Cricetinae , Diafragma/efectos de los fármacos , Fármacos Neuromusculares no Despolarizantes/química , Piperidinas/química , Piridinas/química , Solubilidad , AguaRESUMEN
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.
Asunto(s)
Quelantes/farmacología , Éteres Cíclicos/farmacología , Fármacos Neuromusculares/farmacología , Unión Neuromuscular/efectos de los fármacos , Animales , Aniones/química , Pollos , Trietyoduro de Galamina/farmacología , Concentración 50 Inhibidora , Unión Neuromuscular/fisiología , Fármacos Neuromusculares no Despolarizantes/farmacología , Pancuronio/farmacologíaRESUMEN
A series of oxyanilinium-based AChE inhibitors have been synthesised and tested for the reversal of vecuronium-induced neuromuscular block. Several compounds, for example 2-hydroxy- and 2-methoxy-N,N-dimethyl-N-allylanilinium bromide (3 and 6) showed comparable reversal potencies to edrophonium and clean in vivo cardiovascular profiles.
