Safety and potency of ANQ 9040 in male volunteers.
BACKGROUND
ANQ 9040 is an experimental nondepolarizing neuromuscular relaxant. Initial investigations in animals had indicated a rapid onset of action comparable to that of succinylcholine. The purpose of this study was to assess the safety and potency of ANQ 9040 in humans.


METHODS
ANQ 9040 was assessed in 41 male volunteers. Anesthesia was induced with propofol and maintained with a propofol infusion and 60% N2O/40% O2. Neuromuscular function was measured by mechanomyography using train-of-four stimulation of the ulnar nerve every 12 s. After an initial pilot study, 23 volunteers received a single dose of ANQ 9040 of between 0.5 and 1.1 mg/kg to determine the dose-response relationship. The final 10 volunteers were given twice the estimated ED95 of ANQ 9040 as a single bolus dose.


RESULTS
The estimated ED50 and ED95 of ANQ 9040 were 0.6 and 1.3 mg/kg, respectively. Apart from an increase in heart rate, no important adverse effects were noted after ANQ 9040 administration in the dose range 0.5-1.1 mg/kg. In the volunteers who received 2.6 mg/kg ANQ 9040, a substantial increase in plasma histamine was observed. This was associated with a 12% decrease in mean arterial pressure and a 49% increase in heart rate. In this group, the mean onset time to neuromuscular block was 51.3 s.


CONCLUSIONS
ANQ 9040 is a rapid-onset neuromuscular blocking agent. However, twice the ED95 dose is associated with significant histamine release and tachycardia. This finding suggests that this drug will not be useful in clinical practice.
Munday
I T
IT
Department of Anesthetics, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Jones
R M
RM
Donati
F
F
Mant
T G
TG
Damask
M C
MC
D000293:Adolescent; D000328:Adult; D000731:Androstanes / Q000494:pharmacology*; D001378:Azasteroids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000097:blood; D006801:Humans; D008297:Male; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000097:blood; D012449:Safety
D000731:Androstanes; D001378:Azasteroids; D003473:Neuromuscular Nondepolarizing Agents; D006632:Histamine; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; C085347:ANQ 9040