Relative reinforcing effects of three opioids with different durations of action.
The role of duration of action on the relative reinforcing effects of three opioid drugs (fentanyl, alfentanil, and remifentanil) was evaluated. Duration and onset of action were determined using measures of respiratory depression and antinociception after i.v. administration. Effects on minute volume of respiration indicated that each of the three opioids had immediate onsets of action after i.v. administration. Fentanyl's duration of suppression of respiration and antinociception was longer than that of alfentanil, which was longer than that of remifentanil. Reinforcing strength was measured in i.v. self-administration studies in which the fixed ratio resulting in drug administration was increased from one session to the next. Comparisons were made of the behavioral economic variables P(max) and area under the demand curve (O(max)). Remifentanil maintained higher rates of responding than did alfentanil, and alfentanil maintained higher rates of responding than did fentanyl. When normalized demand functions were compared, however, the drugs did not differ significantly from each other in terms of P(max) or O(max). These data agree with those of others who have suggested that duration of action is not an important contributor to drugs' reinforcing strength.
Ko
M C
MC
Department of Pharmacology and Psychology, University of Michigan, Ann Arbor, Michigan 48109-0632, USA.
Terner
J
J
Hursh
S
S
Woods
J H
JH
Winger
G
G
D015760:Alfentanil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007275:Injections, Intravenous; D008253:Macaca mulatta; D008297:Male; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000077208:Remifentanil; D012119:Respiration / Q000187:drug effects*; D012646:Self Administration
D000701:Analgesics, Opioid; D010880:Piperidines; D015760:Alfentanil; D000077208:Remifentanil; D005283:Fentanyl