Potent reinforcing effects of dihydroetorphine in rats.
Dihydroetorphine is a novel opioid that is an extremely potent analgesic in rodents. The reinforcing potency was determined in rats trained to self-administer heroin and compared to those of fentanyl, heroin, 6-acetylmorphine and morphine for assessment of the abuse potential of dihydroetorphine using a procedure that determines the dose-effect curve in individual sessions. Dihydroetorphine produced a bimodal dose-effect curve similar to that of other opioids. Potency ratios were determined with morphine for the ascending and descending limbs of the dose-effect curve, as well as the dose that yielded maximal response rate. Fentanyl, heroin and 6-acetylmorphine were approximately 100, 8 and 2 times more potent than morphine in maintaining self-administration, respectively. Dihydroetorphine was roughly 1500 to 3000 times more potent than morphine, however, depending upon the limb of the dose-effect curve used for comparison. These potency ratios of dihydroetorphine to morphine were somewhat less than has been reported for analgesia assays, and therefore this compound may have some clinical advantages over other opioids. However, these studies indicate significant abuse liability for dihydroetorphine given its potency in maintaining self-administration in these animals.
Martin
T J
TJ
Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27157-1083, USA. tjmartin@isnet.is.wfu.edu
Kim
S A
SA
Harris
L S
LS
Smith
J E
JE
D000701:Analgesics, Opioid; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005048:Etorphine / Q000031:analogs & derivatives*; D005283:Fentanyl; D003932:Heroin; D008297:Male; D009020:Morphine; D009022:Morphine Derivatives; D051381:Rats; D011916:Rats, Inbred F344; D013375:Substance Withdrawal Syndrome; D019966:Substance-Related Disorders
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; D005048:Etorphine; D003932:Heroin; D009020:Morphine; C026979:6-O-monoacetylmorphine; C034765:18,19-dihydroetorphine; D005283:Fentanyl