RT Journal Article
SR Electronic
T1 Buprenorphine, morphine and naloxone effects during ascending morphine maintenance in humans.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 836
OP 846
VO 278
IS 2
A1 K J Schuh
A1 S L Walsh
A1 G E Bigelow
A1 K L Preston
A1 M L Stitzer
YR 1996
UL http://jpet.aspetjournals.org/content/278/2/836.abstract
AB One purpose of this study was to characterize the acute effects of the partial mu-opioid agonist buprenorphine administered to human subjects undergoing maintenance treatment with ascending doses of morphine. A second purpose was to examine the development of tolerance, cross-tolerance and physical dependence under the same morphine maintenance conditions. Six opioid-dependent volunteers were treated chronically with ascending morphine doses of 15, 30, 60 and 120 mg/day. Each morphine dosing level was maintained for 2 weeks, with test drugs administered during the second week of maintenance of each morphine dose. Both morphine (30 mg i.m.) and buprenorphine (6 mg i.m.) constricted pupils and produced reports of opioid-like subjective effects. The magnitude of these effects was inversely related to the morphine maintenance dose, with no effects being detected at higher maintenance levels. Naloxone (0.3 mg) produced little effect at lower morphine maintenance doses but precipitated withdrawal at higher maintenance doses. Buprenorphine failed to precipitate withdrawal even when subjects were treated with 120 mg/day morphine. These findings indicate that dose-dependent tolerance to morphine, cross-tolerance to buprenorphine and physical dependence develop during morphine maintenance. The finding that buprenorphine does not act as an antagonist under these dosing conditions further supports the clinical observation that there are conditions under which patients dependent on short-acting opioids can be comfortably transferred directly to buprenorphine maintenance treatment.