A-3665, a new short-acting opioid: a comparison with alfentanil.
A-3665 is a new short-acting synthetic opioid of the piperidine class. We conducted a double-blind, escalating dose comparison of A-3665 to alfentanil and placebo. Analgesic efficacy was assessed after the administration of A-3665 in increasing intravenous doses (0.25, 0.5, 1, 2, 4, 8, 16, 32, and 64 micrograms/kg) to nine groups of volunteers. At the lower doses (0.25, 0.5, 1, and 2 micrograms/kg), five volunteers were in each group; four received A-3665 and one received placebo in a double-blind manner. There were nine volunteers in each of the next three groups; four received A-3665 (4, 8, or 16 micrograms/kg), four received alfentanil (4, 8, or 16 micrograms/kg), and one received placebo. At the 32 micrograms/kg and 64 micrograms/kg dose levels, five subjects each were to be enrolled (four to receive A-3665 and one to receive placebo); however, the study was terminated after two subjects in the 64 micrograms/kg group had significant respiratory depression. Both drugs caused potent analgesia, compared with placebo, with peak effect occurring 3 min after injection. There was no significant difference in analgesic potency of A-3665 and alfentanil as measured by tolerance to tibial pressure at 3 min. At the dose of 16 micrograms/kg, both drugs significantly increased pain tolerance to tibial pressure compared with placebo at 3 min, but alfentanil continued to display significant analgesic effect versus placebo and versus A-3665 at 6, 11, and 15 min after injection. A-3665 caused significant respiratory depression at doses of 32 micrograms/kg and 64 micrograms/kg, but alfentanil did not induce significant respiratory depression at the doses tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Cambareri
J J
JJ
Department of Anesthesiology, SUNY Health Science Center, Syracuse 13210.
Afifi
M S
MS
Glass
P S
PS
Esposito
B F
BF
Camporesi
E M
EM
D000293:Adolescent; D000328:Adult; D015760:Alfentanil / Q000009:adverse effects / Q000494:pharmacology*; D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000502:physiology; D002319:Cardiovascular System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006632:Histamine / Q000097:blood; D006801:Humans; D010100:Oxygen / Q000502:physiology; D010146:Pain / Q000188:drug therapy; D010313:Partial Pressure; D010880:Piperidines / Q000009:adverse effects / Q000494:pharmacology*; D012119:Respiration / Q000187:drug effects; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology*
D000700:Analgesics; D010880:Piperidines; D013777:Tetrazoles; D002245:Carbon Dioxide; D015760:Alfentanil; C080498:trefentanil; D006632:Histamine; D010100:Oxygen