The partial opioid agonist, buprenorphine, protects against lethal effects of cocaine.
Buprenorphine (0.3-3.0 mg/kg) produced dose-dependent protection against the lethal effects of cocaine in mice. The (+)-enantiomer of buprenorphine did not protect up to doses over 100 times greater than the lowest effective dose of its (-)-enantiomer. The protective effects were also produced by the opioid agonists morphine and methadone, but not by the opioid antagonist, naltrexone. Low doses of naltrexone (0.3-1.0 mg/kg) blocked the protective effects of buprenorphine. Protection conferred by buprenorphine was not observed in CXBK mice, a recombinant inbred strain relatively devoid of mu-opioid receptors. Thus, buprenorphine appears to protect against the lethal effects of cocaine by a process mediated by mu-opioid receptors. The present results should provide some additional safety assurance in future clinical trials with buprenorphine, especially in outpatient trials where cocaine abuse may continue along with treatment.
Witkin
J M
JM
Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.
Johnson
R E
RE
Jaffe
J H
JH
Goldberg
S R
SR
Grayson
N A
NA
Rice
K C
KC
Katz
J L
JL
D000818:Animals; D001921:Brain / Q000187:drug effects; D002047:Buprenorphine / Q000494:pharmacology*; D003042:Cocaine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008691:Methadone / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects; D017450:Receptors, Opioid, mu; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control
D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D002047:Buprenorphine; D009271:Naltrexone; D009020:Morphine; D003042:Cocaine; D008691:Methadone