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 onse t of action comparable to that of succinylcholine. The purpose of this study was to assess the safety and potency of ANQ 9040 in humans. Met hods: ANQ 9040 was assessed in 41 male volunteers. Anesthesia was indu ced with propofol and maintained with a propofol infusion and 60% N2O/ 40% O-2. Neuromuscular function was measured by mechanomyography using train-of-four stimulation of the ulnar nerve every 12 s. After an ini tial 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 ED(95) of ANQ 9040 as a single bolus dose. Results: The estimated ED(50) and ED(95) of ANQ 9040 were 0.6 and 1.3 mg/kg, respectively. Apart from an increa se in heart rate, no important adverse effects were noted after ANQ 90 40 administration in the dose range 0.5-1.1 mg/kg. In the volunteers w ho received 2.6 mg/kg ANQ 9040, a substantial increase in plasma hista mine was observed. This was associated with a 12% decrease in mean art erial pressure and a 49% increase in heart rate. In this group, the me an onset time to neuromuscular block was 51.3 s. Conclusions: ANQ 9040 is a rapid-onset neuromuscular blocking agent. However, twice the ED( 95) dose is associated with significant histamine release and tachycar dia. This finding suggests that this drug will not be useful in clinic al practice.