The characteristics of the hypothetical ideal neuromuscular
blocking drug are described and some of the unwanted effects of the
older muscle relaxants are reviewed. The history behind the
development of short acting rapid onset non-depolarising
neuromuscular blockers is outlined. Attention is focused on the
benzylisoquinolinium compounds. The development of atracurium, the
animal pharmacology and the preliminary studies in man are
discussed.Patient studies are performed to investigate how closely the
pharmacological characteristics of atracurium relate to those of
the ideal drug. Some potential clinical uses for atracurium are
investigated.Atracurium is noted to have an onset time significantly slower than
suxamethonium. Onset time and duration are found to vary with the
mode of neuromuscular monitoring and anaesthetic depth. When 0.6
mg kg"' atracurium is injected rapidly, there is a significant
elevation in serum histamine concentration. The associated
haemodynamic response may be attenuated by slowing the speed of
injection or by pretreating with intravenous HI and H2 antagonists.
Onset time may be shortened by using 0.8 mg kg"' but at the expense
of a transient drop in blood pressure and increase in heart rate
unless administration is slowed. Priming provides no improvement
in onset time, nor in haemodynamic stability. Atracurium shows no
tendency to cumulate when administered as an infusion. The
pharmacodynamics and pharmacokinetics of atracurium in anephric
patients are found to be very similar to those of healthy patients.
Pretreatment with atracurium does not prevent postoperative
suxamethonium myalgia. When suxamethonium is administered during a
recovering atracurium block, very high doses of suxamethonium are
required to produce 100% blockade of the twitch. The response to
atracurium by patients with myasthenia gravis is described.Initial studies with two further benzylisoquinolinium compounds are
reportedBWB1090U is a benzylisoquinolinium non-depolarising muscle relaxant
hydrolysed by plasma cholinesterase. The initial laboratory
studies with Rhesus monkeys and the neuromuscular and
cardiovascular effects on volunteers are reported. BWB1090U
appears to be a potent drug with a short duration, minimal
cumulative activity and reasonable cardiovascular stability. The
transient changes observed in the haemodynamic parameters are
thought to be due to histamine release.BWA938U is discussed and the first pilot study is described. The
first study in patients in Europe is also reported. BWA938U
appears to be a very potent long acting non-depolarising blocking
drug devoid of haemodynamic effects. It is well reversed with
neostigmine but not by edrophonium.Finally, current and future research in the development of new,
rapid onset, short acting neuromuscular blocking agents is
discussed
