The pharn~acodynamics and pharmacokinelics oJ" a new nondepolarizing neuromuscular blocking agent, Ore 9426, were investigated. Ten patients undergoing elective head and neck surgery and anaesthetized with nitrous oxide', halothane and fentanyl, received a bolus dose of Ore 9426 (I rag. kg -t , 3 x EDgo

SummaryOrg 9426 is a new nondepolarising neuromuscular blocking agent with a chemical structure related to that of vecuronium, as shown in Figure 1.From recent clinical studies Org 9426 appeared to be five to seven times less potent than vecuronium and showed a faster rate of onset of neuromuscular block [I, 21, whereas duration of action and recovery index were found to be similar [2]. Good to excellent intubation conditions were shown within 60 s after approximately 1.5 times the ED,,, dose [2]. Org 9426, available in a 'ready for use' pharmaceutical presentation, when administered in the clinical dose range, demonstrated no relevant cardiovascular or other side effects either in man [I-31 or animals [4, 51. This study was designed to evaluate the potency, time course of action, reversibility, cumulative tendency and cardiovascular effects of Org 9426 in patients anaesthetised with five different techniques: nitrous oxide (65%) in oxygen with halothane, enflurane, isoflurane, droperidol/fentanyl or propofol/fentanyl. Methods Patients 0 II

VAN DEN BROEK L, LAMBALK LM, RICHARDSON FJ, WIERDA JMKH. Dose-response relation, neuromuscular blocking action, intubation conditions, and cardiovascular effects of Org 9273, a new neuromuscular blocking agent. Anesth Analg 1991;72:811-6. The ED,, and the ED,,, the time-course of the neuromuscular block, the intubation conditions, and the cardiovascular effects of Org 9273, a new steroidal nondepolarizing neuromuscular blocking agent, have been evaluated in 41 anesthetized patients. From cumulative dose-response curves the ED,, and ED,, were calculated to be 175 and 300 pglkg, respectively. The time-course of neuromuscular blockade after 300-and 500-pglkg doses of Org 9273 appeared to be similar to that of equipotent doses of vecuronium. The neuromuscular block was characterized by a fast initial rate of block development. High-dose Org 9273(1 mglkg = 3 4 times the ED,,) had a clinical duration comparable to an intubating dose of pancuronium, but a considerably more rapid onset and recovery index. Three hundred micrograms per kilogram and 500 pglkg Org 9273 produced good to excellent intubation conditions 1 min after administration. Org 9273 in a dose of 0.5-2 times the ED,, produced no cardiovascular changes; however, 3 4 times the ED,, increased heart rate 20%-25% (P < 0.001), probably due to a vagolytic effect.Key Words: NEUROMUSCULAR RELAXANT, Org 9273.As a result of the search for a nondepolarizing neuromuscular blocking agent as an alternative to succinylcholine for intubation and short surgical procedures, some new neuromuscular blocking agents have recently become available for clinical trials. One of these agents is Org 9273, the 2-morpholino, 3-desacetyl analogue of vecuronium (Figure l), which has been shown to be stable in aqueous solution.Preliminary animal studies (1,2) show that Org 9273 is 3-5 times less potent than vecuronium but with a faster onset of action and a similar duration of action. Furthermore, Org 9273 in doses of 1-3 times the ED90 produces only minor changes in heart rate and blood pressure in experimental animals.We have performed a dose-finding study to investigate the dose-response relationship, the time-course of neuromuscular blocking action, the intubation conditions, and the hemodynamic stability of Org 9273 in anesthetized patients. MethodsThe study was approved by the local medical ethical committee. Forty-one ASA physical status I and I1 patients, aged 18-60 yr, scheduled for elective surgery, participated in this study after they had given written informed consent.After oral premedication with 7.5 mg midazolam approximately 60 min before the expected start of anesthesia, anesthesia was induced with 1-5 &kg fentanyl and 3-7 mg/kg thiopental. After tracheal intubation, anesthesia was maintained with halothane, 0.5% inspiratory concentration, in a 2:l mixture Of nitrous Oxide and Oxygen and increments of 50-100 pg fentanyl. End-tidal k o 2 was kept between 32 and 42 mm Hg. After 290% recovery from the Org 9273 vecuronium was to maintain muscle relaxation if necessary. Cent...