Assuntos
Androstanóis/química , Ciclodextrinas/química , Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes/química , gama-Ciclodextrinas , Androstanóis/farmacologia , Animais , Cristalografia por Raios X , Ciclodextrinas/farmacologia , Diafragma/efeitos dos fármacos , Diafragma/inervação , Técnicas In Vitro , Macaca mulatta , Camundongos , Modelos Moleculares , Contração Muscular/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Rocurônio , SugammadexRESUMO
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.
Assuntos
Acetilcolinesterase/efeitos dos fármacos , Compostos Alílicos/farmacologia , Compostos de Anilina/farmacologia , Inibidores da Colinesterase/farmacologia , Edrofônio/antagonistas & inibidores , Bloqueadores Neuromusculares/antagonistas & inibidores , Compostos Alílicos/química , Compostos de Anilina/química , Cristalografia por Raios X , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Quelantes/farmacologia , Éteres Cíclicos/farmacologia , Fármacos Neuromusculares/farmacologia , Junção Neuromuscular/efeitos dos fármacos , Animais , Ânions/química , Galinhas , Trietiodeto de Galamina/farmacologia , Concentração Inibidora 50 , Junção Neuromuscular/fisiologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Pancurônio/farmacologiaRESUMO
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.
Assuntos
Acetilcolinesterase/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Indanos/farmacologia , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Piperidinas/farmacologia , Brometo de Vecurônio/antagonistas & inibidores , Inibidores da Colinesterase/química , Donepezila , Indanos/química , Piperidinas/químicaRESUMO
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.