Reversal by suramin of neuromuscular block produced by pancuronium in the anaesthetized rat.
1. Rats were anaesthetized with sodium pentobarbitone and maximal twitches of a tibialis anterior muscle were evoked by stimulation of the motor nerve. 2. Suramin, injected intravenously in a series of cumulative bolus doses, each 15 mg kg-1, completely reversed a 90% depression of twitches maintained by a continuous intravenous infusion of pancuronium. The cumulated dose necessary to restore twitches to 50% of their control amplitude was 35 mg kg-1. Suramin did not modify a similar degree of block produced by suxamethonium, nor did it affect the amplitude of control maximal twitches, even in cumulative doses up to 150 mg kg-1. 3. The effects of bolus doses of suramin (85 mg kg-1), neostigmine (0.03 mg kg-1) and 4-aminopyridine (1.2 mg kg-1), calculated to restore pancuronium-blocked twitches to 95% of control amplitude, were compared. Suramin produced the most rapid reversal (1.1 +/- 0.5 min), but its duration of action was the shortest (9.4 +/- 1.6 min). Suramin was without effect on heart rate or blood pressure in the doses used. 4. The results showed that suramin reversed neuromuscular block produced by nondepolarizing blocking drug, pancuronium, but was without effect on a block produced by the depolarizing blocking drug, suxamethonium. Its short duration of action suggests that suramin would probably not be of value clinically as a reversal agent. However, it is possible that it might serve as a starter compound for the synthesis and development of a new class of reversal agents for use in anaesthetic practice.
Henning
R H
RH
Department of Pharmacology/Clinical Pharmacology, University of Groningen, The Netherlands.
Nelemans
A
A
Houwertjes
M
M
Agoston
S
S
D015761:4-Aminopyridine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D004558:Electric Stimulation; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009388:Neostigmine / Q000494:pharmacology; D009466:Neuromuscular Blocking Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010197:Pancuronium / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013390:Succinylcholine / Q000494:pharmacology; D013498:Suramin / Q000494:pharmacology*
D009466:Neuromuscular Blocking Agents; D009388:Neostigmine; D013498:Suramin; D015761:4-Aminopyridine; D013390:Succinylcholine; D010197:Pancuronium