Opioid and Non-opioid Actions of Novel Fentanyl Derivatives in Rhesus Monkey Analgesia and Mouse Vas Deferentia Studies
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Authors
Flynn, Diana
Issue Date
1992
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Four fentanyl derivatives recently developed in the 4-(heteroanilido)-piperidine series
(ANQ 3463, 3326, 3296 and 3295) have the potential to be clinically important
analgesics. All test compounds were studied in the rhesus monkey (Macaca mulatta)
to evaluate the analgesic effects of each compound. Preliminary studies of drugs
were also made in isolated mouse vas deferentia because it is a simpler model for
drug classification than the whole animal model. In analgesia studies, all fentanyl
derivatives were potent analgesics with little associated respiratory or cardiac
depression. In addition, test compounds antagonized the respiratory depressant effects
of large doses of alfentanil. Results of this study demonstrate that small structural
changes in the parent compound fentanyl produce significant differences in the agonist
and antagonist actions of these compounds. For example, opioid analgesia was
observed with ANQ 3463, that was attenuated by naltrexone in a manner consistent
with mu receptor mediation, while ANQ 3326 and ANQ 3296 produced both opioid
and non-opioid analgesia. In addition, acute doses of both compol:lnds antagonized
the analgesic effects of alfentanil. ANQ 3295 had only non-opioid agonist effects and
opioid antagonist effects in analgesia studies. ANQ 3295 in small doses was similar
to the opioid antagonist naltrexone. Results obtained in the isolated mouse vas
deferens studies support the opioid and non-opioid characterizations of ANQ 3463,
3326 and 3296 found in the analgesia studies. However, in isolated tissue ANQ 3295
produced some opioid agonist actions which were not observed in analgesia studies.
Description
iv, 45 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.