A-3665, a new short-acting opioid: a comparison with alfentanil.

Abstract

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)

• Authors: J J Cambareri, M S Afifi, P S Glass, B F Esposito, E M Camporesi
• Journal: Anesthesia and analgesia (Anesth Analg) Vol. 76 Issue 4 Pg. 812-6 (Apr 1993) ISSN: 0003-2999 [Print] United States
• PMID: 8466023 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Piperidines
• Tetrazoles
• Carbon Dioxide
• Alfentanil
• trefentanil
• Histamine
• Oxygen

Topics

• Adolescent
• Adult
• Alfentanil (adverse effects, pharmacology)
• Analgesics (adverse effects, pharmacology)
• Carbon Dioxide (physiology)
• Cardiovascular System (drug effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Histamine (blood)
• Humans
• Oxygen (physiology)
• Pain (drug therapy)
• Partial Pressure
• Piperidines (adverse effects, pharmacology)
• Respiration (drug effects)
• Tetrazoles (adverse effects, pharmacology)