[Experimental study on the principal effects and dependence potential of thiofentanil].
Thiofentanil is a synthetic analgesic with pharmacological effects similar to etorphine hydrochloride (M99). The aim of the present study was to assess its analgesic and immobilization effects and to evaluate its dependence potential in comparison with morphine. The median analgesic dose (AD50) was measured by hot plate method in mice. The median paralytic dose (PD50), as an indicator of immobilization, was tested in rats, rabbits, dogs and monkeys. Results showed that the analgesic potency of this drug was 3260 times that of morphine, 22 times that of fentanyl and 1.5 times that of M99 and the immobilization effect was 2-3 times that of M99. Results from jumping test in mice and physical dependence-producing test in rats (the drug was dissolved in drinking water) showed that thiofentanil possessed physical dependence liability weaker than morphine. Physical dependence was not observed in rats with intravenous injection of one dose each h over a period of 72 h, and also in monkey with 20-week drug medication. The LD50 of thiofentanil was also determined in mice, rats, rabbits, dogs and monkeys in comparison with M99. Results suggest that it should be valuable to develop thiofentanil as an analgesic for clinical use.
National Institute on Drug Dependence, Beijing Medical University.
M
M
Li
J W
JW
Zheng
Y H
YH
Liu
J L
JL
Zhang
L N
LN
Liu
Z J
ZJ
Cai
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D005260:Female; D007103:Immobilization; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D010146:Pain / Q000503:physiopathology*; D010880:Piperidines / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D012684:Sensory Thresholds / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000209:etiology; D019966:Substance-Related Disorders / Q000209:etiology; D013844:Thiazoles / Q000494:pharmacology* / Q000633:toxicity
D000701:Analgesics, Opioid; D010880:Piperidines; D013844:Thiazoles; C071584:thiofentanil oxalate