Antinociceptive Activity of the Novel Fentanyl Analogue iso-Carfentanil in Rats

A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful antinociceptive drugs. In this study, the newly synthesized fentanyl analogue 3-carbomethoxy fentanyl (iso-carfentanil) was compared to...

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Bibliographic Details
Published in:Japanese journal of pharmacology 2000, Vol.84(2), pp.188-195
Main Authors: Vučković, Sonja, Prostran, Milica, Ivanović, Milovan, Ristović, Zorana, Stojanović, Radan
Format: Article
Language:English
Subjects:
Analgesics - chemical synthesis
Analgesics - chemistry
Analgesics - pharmacology
Animals
Antinociception
Carfentanil
Drug Interactions
Female
Fentanyl
Fentanyl - chemical synthesis
Fentanyl - chemistry
Fentanyl - pharmacology
Infusions, Parenteral
Male
Naloxone - pharmacology
Pain Measurement
Rats
Rats, Wistar
Structure-Activity Relationship
Time Factors
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Summary:A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clinically useful antinociceptive drugs. In this study, the newly synthesized fentanyl analogue 3-carbomethoxy fentanyl (iso-carfentanil) was compared to fentanyl for its antinociceptive activity (tail-immersion test) in rats. It was revealed that the introduction of a 3-carbomethoxy group in the piperidine ring of fentanyl skeleton reduced the potency and shortened the duration of action of the parent compound, i.e., fentanyl. The antinociceptive potency of 3-carbomethoxy fentanyl is influenced mainly by the steric factor (voluminosity of the carbomethoxy group and the cis/trans isomerism), while the chemical nature of the group is probably irrelevant. This is in agreement with SAR studies of other 3-substituted fentanyl analogues. In contrast to potency, the duration of action is not affected by cis/trans isomerism. It is assumed that the time course of action of 3-carbomethoxy fentanyl is influenced by the nature of the carbomethoxy group. Since the potency and the duration of action of this novel antinociceptive compound are interesting from the aspect of SAR studies and have potential promise for clinical application, 3-carbomethoxy fentanyl deserves to be extensively evaluated.
ISSN:0021-5198
1347-3506
DOI:10.1254/jjp.84.188