COMPARATIVE EFFECTS OF VELNACRINE, TACRINE AND PHYSOSTIGMINE ON THE TWITCH RESPONSES IN THE RAT PHRENIC-HEMIDIAPHRAGM PREPARATION

1. Cholinesterase inhibitors potentiated twitch responses induced by n erve stimulation, with physostigmine more potent than tacrine and veln acrine. However, at higher concentrations, tacrine decreased twitch re sponses in a concentration-dependent manner. 2. Tacrine strongly depre ssed directly-induced twitch responses, whereas the other drugs had mi nimal effects. 3. Physostigmine was the most potent drug in reversal o f 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 skel etal neuromuscular transmission. Additionally, the blocking effects of tacrine could limit its therapeutic efficacy.