Neuromuscular blocking activity of bis-4-benzyltetrahydroisoquinolinium esters in the cat

The purpose of this work was to identify a new ultra-short-acting neuromuscular blocking agent devoid of the potential to produce histamine-like cardiovascular effects at ≥ED95 doses. Eight new bis-4-benzyltetrahydroisoquinolinium esters, derivatives of (E)-oct-4-ene-1,8-dioyl acid, were tested for neuromuscular blocking activity in the cat and compared with mivacurium chloride. All compounds were more than ten times less potent than mivacurium but exhibited a rapid onset of action (≊0.9–1.8 min from injection to maximum neuromuscular block) and an ultra-short duration of neuromuscular block (≊5–8 min from injection to 95% recovery) at approximately ED95 doses; however, at these and even lesser doses, they also produced histamine-like cardiovascular effects and inhibited the response to vagal stimulation. The data suggest that, in the benzyltetrahydroisoquinolinium class of neuromuscular blocking agents, 4-benzyl substitution may offer the desired rapid onset and ultra-short duration of action at ED95 doses, but these advantages are offset by the adverse cardiovascular and autonomic effects which occur at ≤ED95 doses.