Comparative effects of velnacrine, tacrine and physostigmine on the twitch responses in the rat phrenic-hemidiaphragm preparation

Gen Pharmacol. 1993 Sep;24(5):1101-5. doi: 10.1016/0306-3623(93)90356-3.

Abstract

1. Cholinesterase inhibitors potentiated twitch responses induced by nerve stimulation, with physostigmine more potent than tacrine and velnacrine. However, at higher concentrations, tacrine decreased twitch responses in a concentration-dependent manner. 2. Tacrine strongly depressed directly-induced twitch responses, whereas the other drugs had minimal effects. 3. Physostigmine was the most potent drug in reversal of tubocurarine-induced blockade, but its antagonism index was similar to those obtained with tacrine and velnacrine at higher concentrations. When evaluating their ability to reverse neomycin-induced blockade, all drugs exhibited a similar effect. 4. It is concluded that tacrine and velnacrine are less potent than physostigmine in potentiating skeletal neuromuscular transmission. Additionally, the blocking effects of tacrine could limit its therapeutic efficacy.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholinesterase Inhibitors / pharmacology*
  • Electric Stimulation
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Neuromuscular Blocking Agents / pharmacology
  • Neuromuscular Junction / drug effects*
  • Neuromuscular Junction / physiology
  • Phrenic Nerve / drug effects*
  • Phrenic Nerve / physiology
  • Physostigmine / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Muscles / drug effects*
  • Respiratory Muscles / physiology
  • Tacrine / analogs & derivatives
  • Tacrine / pharmacology

Substances

  • Cholinesterase Inhibitors
  • Neuromuscular Blocking Agents
  • Tacrine
  • Physostigmine
  • velnacrine