TY - JOUR
T1 - Buprenorphine and methoclocinnamox
T2 - Agonist and antagonist effects on respiratory function in rhesus monkeys
AU - Kishioka, Shiroh
AU - Paronis, Carol A.
AU - Lewis, John W.
AU - Woods, James H.
PY - 2000/3/17
Y1 - 2000/3/17
N2 - Buprenorphine and methoclocinnamox are partial μ-opioid receptor agonists with potential use in the treatment of opioid abuse. The ability of these drugs to suppress respiration as well as their ability to antagonize the respiratory suppressant effects of morphine and heroin were tested in rhesus monkeys. Frequency (f), minute volume (V(e)) tidal volume (V(t)) in monkeys breathing air or 5% CO2 in air were recorded using a pressure-displacement plethysmograph. Buprenorphine (0.001-10 mg/kg) produced a dose-dependent decrease in respiratory parameters that plateaued at a dose of 1 mg/kg in both air and 5% CO2. Methoclocinnamox (0.032-1 mg/kg) also produced dose-dependent respiratory depression that plateaued at a dose of 0.3 mg/kg in air, and was directly related to dose in 5% CO2. Respiratory suppression produced by buprenorphine 1 and 10 mg/kg lasted for 3 and 7 days, respectively, whereas the suppression produced by the largest dose of methoclocinnamox (1 mg/kg, the solubility limit) lasted less than 24 h. Buprenorphine and methoclocinnamox antagonized morphine- and heroin-induced respiratory depression, and this antagonist effect was observed concomitantly with, as well as following, the μ-opioid receptor agonist effects of buprenorphine and methoclocinnamox. The μ-opioid receptor antagonist effects of buprenorphine (10 mg/kg) and methoclocinnamox (1 mg/kg) lasted for 2 weeks. These results suggest that buprenorphine and methoclocinnamox have a wide margin of safety in clinical use and that these two compounds have a prolonged, insurmountable, μ-opioid receptor antagonist effect after the disappearance of their agonist effects. Copyright (C) 2000 Elsevier Science B.V.
AB - Buprenorphine and methoclocinnamox are partial μ-opioid receptor agonists with potential use in the treatment of opioid abuse. The ability of these drugs to suppress respiration as well as their ability to antagonize the respiratory suppressant effects of morphine and heroin were tested in rhesus monkeys. Frequency (f), minute volume (V(e)) tidal volume (V(t)) in monkeys breathing air or 5% CO2 in air were recorded using a pressure-displacement plethysmograph. Buprenorphine (0.001-10 mg/kg) produced a dose-dependent decrease in respiratory parameters that plateaued at a dose of 1 mg/kg in both air and 5% CO2. Methoclocinnamox (0.032-1 mg/kg) also produced dose-dependent respiratory depression that plateaued at a dose of 0.3 mg/kg in air, and was directly related to dose in 5% CO2. Respiratory suppression produced by buprenorphine 1 and 10 mg/kg lasted for 3 and 7 days, respectively, whereas the suppression produced by the largest dose of methoclocinnamox (1 mg/kg, the solubility limit) lasted less than 24 h. Buprenorphine and methoclocinnamox antagonized morphine- and heroin-induced respiratory depression, and this antagonist effect was observed concomitantly with, as well as following, the μ-opioid receptor agonist effects of buprenorphine and methoclocinnamox. The μ-opioid receptor antagonist effects of buprenorphine (10 mg/kg) and methoclocinnamox (1 mg/kg) lasted for 2 weeks. These results suggest that buprenorphine and methoclocinnamox have a wide margin of safety in clinical use and that these two compounds have a prolonged, insurmountable, μ-opioid receptor antagonist effect after the disappearance of their agonist effects. Copyright (C) 2000 Elsevier Science B.V.
KW - (Rhesus monkey)
KW - Buprenorphine
KW - Methoclocinnamox
KW - Opioid receptor agonist
KW - Opioid receptor antagonist
KW - Respiration
UR - http://www.scopus.com/inward/record.url?scp=0034677963&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034677963&partnerID=8YFLogxK
U2 - 10.1016/S0014-2999(00)00039-X
DO - 10.1016/S0014-2999(00)00039-X
M3 - Article
C2 - 10729371
AN - SCOPUS:0034677963
VL - 391
SP - 289
EP - 297
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 3
ER -