EFFICACY OF METHYLNALTREXONE VERSUS NALOXONE FOR REVERSAL OF MORPHINE-INDUCED DEPRESSION OF HYPOXIC VENTILATORY RESPONSE

Methylnaltrexone (MNTX) is a quaternary derivative of naltrexone. It d oes not cross the blood-brain barrier and, thus, it reverses periphera lly mediated effects of morphine without blocking its centrally locate d analgesic effects. The effects of MNTX on morphine-induced depressio n of hypoxic ventilatory response are unknown. We evaluated the effica cy of MNTX, compared with naloxone, in reversing this effect. On three sessions separated by a week, 10 healthy male volunteers received mor phine, 0.125 mg/kg, as a bolus at 20 min after completing a control hy poxic ventilatory challenge. At 60 min, naloxone, 5 mug/kg, MNTX, 0.3 mg/kg, or placebo was administered in a randomized double-blind order. Four isocapnic hypoxic ventilatory challenges were conducted: 0 min ( control), 40 min (postmorphine), and 80 and 120 min (postreversal) and the hypoxic respiratory responses were recorded. Morphine administrat ion was associated with a significant depression in hypoxic responses: The slope of the response (L/min/SpO2) and the predicted ventilation at 80% O2 saturation (VE80) (L/min) decreased significantly in the thr ee sessions (P < 0.05). Naloxone injection reversed the respiratory de pression at 80 min (85% of the control value of the slope and 89% of V E80), whereas MNTX and placebo did not. At 120 min, the slope (69%) an d VE80 (80%) after naloxone administration were not significantly diff erent from control. MNTX slope (69%) was not statistically different f rom the control, whereas VE80 (70%) was still depressed (P < 0.05). Pl acebo slope and VE80, at 120 min, remained lower than the control (P < 0.05). These data show that MNTX is not as effective as naloxone for reversal of morphine-mediated depression of respiration during acute h ypoxia.