Antagonism of acute cocaine toxicity by buprenorphine.
The effect of buprenorphine pretreatment on the acute cocaine toxicity was assessed in male Swiss Webster mice. Buprenorphine pretreatment (0.15 or 0.30 mg/kg ip, 30 mins before) significantly attenuated the lethal effects of cocaine (60-140 mg/kg ip). The dose of cocaine which resulted in 50% mortality (LD50) in saline pretreated group was 100.61 mg/kg while the LD50 of cocaine in buprenorphine (0.15 and 0.3 mg/kg) pretreated groups were 113.57 and 118.16 mg/kg respectively. There was no significant change in the ratio of brain/plasma levels of cocaine in buprenorphine pretreated group when compared to the ratio from saline treated controls. Furthermore, neither naloxone (10 mg/kg ip, 15 mins before) nor naltrexone (3 mg/kg ip, 15 mins before) pretreatment affected the LD50 of cocaine. When tested 0.5, 1, 2, 4, 8 and 24 hrs after cocaine administration, sublethal dose of cocaine (80 mg/kg ip) injection resulted in significant increase in the plasma lactate dehydrogenase (LDH) levels. Buprenorphine pretreatment significantly attenuated cocaine-induced release of LDH. These results suggest that buprenorphine could be of potential advantage over naloxone in the management of cocaine and heroin ("speed ball") toxicity and in studies on the pharmacotherapy of cocaine-induced toxicity, LDH levels may be used as a biochemical marker to assess the protective effects of drugs.
Shukla
V K
VK
Department of Anesthesiology, New York University Medical Center, NY 10016.
Goldfrank
L R
LR
Turndorf
H
H
Bansinath
M
M
D000704:Analysis of Variance; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology
D009270:Naloxone; D002047:Buprenorphine; D009271:Naltrexone; D007770:L-Lactate Dehydrogenase; D003042:Cocaine