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The relationship between the concentration of ambenonium (AMB), a selective and reversible acetylcholinesterase (AChE) inhibitor, in plasma and the potentiation of contractile muscle tension was investigated using a sciatic nerve-muscle preparation of rat. The developed isometric contraction was enhanced dose-dependently after i.v. administration of low doses (5-20 nmol/kg) of AMB, but the contraction was weakened when AMB was administered at high doses (100-1000 nmol/kg), and the concentration-effect relationship was bell-shaped. The muscle contraction profile after 50 nmol/kg administration without previous administration, with 20 nmol/kg and with 50 nmol/kg administered previously were quite different from each other. These findings suggest that the potentiation of contractile muscle tension by AMB may be acutely tolerated and the concentration-effect relationship may change time-dependently.

Appearance of Tolerance in the Increase of Contractile Muscle Tension by Ambenonium in Rats.