Novel piperidinium and pyridinium agents as water-soluble acetylcholinesterase inhibitors for the reversal of neuromuscular blockade

Bioorg Med Chem Lett. 2002 Sep 16;12(18):2569-72. doi: 10.1016/s0960-894x(02)00483-3.

Abstract

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.

MeSH terms

  • Acetylcholinesterase / drug effects*
  • Animals
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology*
  • Cricetinae
  • Diaphragm / drug effects
  • Neuromuscular Nondepolarizing Agents / chemistry
  • Neuromuscular Nondepolarizing Agents / pharmacology*
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Solubility
  • Vecuronium Bromide / antagonists & inhibitors*
  • Water

Substances

  • Cholinesterase Inhibitors
  • Neuromuscular Nondepolarizing Agents
  • Piperidines
  • Pyridines
  • Water
  • Vecuronium Bromide
  • Acetylcholinesterase