Efficacy of methylnaltrexone versus naloxone for reversal of morphine-induced depression of hypoxic ventilatory response.
Methylnaltrexone (MNTX) is a quaternary derivative of naltrexone. It does not cross the blood-brain barrier and, thus, it reverses peripherally mediated effects of morphine without blocking its centrally located analgesic effects. The effects of MNTX on morphine-induced depression of hypoxic ventilatory response are unknown. We evaluated the efficacy of MNTX, compared with naloxone, in reversing this effect. On three sessions separated by a week, 10 healthy male volunteers received morphine, 0.125 mg/kg, as a bolus at 20 min after completing a control hypoxic ventilatory challenge. At 60 min, naloxone, 5 micrograms/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 administration 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 three sessions (P < 0.05). Naloxone injection reversed the respiratory depression at 80 min (85% of the control value of the slope and 89% of VE80), whereas MNTX and placebo did not. At 120 min, the slope (69%) and VE80 (80%) after naloxone administration were not significantly different from control. MNTX slope (69%) was not statistically different from the control, whereas VE80 (70%) was still depressed (P < 0.05). Placebo 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 hypoxia.
Amin
H M
HM
Department of Anesthesiology, State University of New York Health Science Center, Syracuse 13210.
Sopchak
A M
AM
Foss
J F
JF
Esposito
B F
BF
Roizen
M F
MF
Camporesi
E M
EM
D000328:Adult; D004311:Double-Blind Method; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors*; D009270:Naloxone / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds; D012119:Respiration / Q000502:physiology*
D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009270:Naloxone; D009271:Naltrexone; D009020:Morphine