Antinociceptive activity of the novel fentanyl analogue iso-carfentanil inrats

A large number of fentanyl analogues have been synthesized so far, both to establish the structure-activity-relationship (SAR) and to find novel, clin ically useful antinociceptive drugs. In this study, the newly synthesized f entanyl 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 piperi dine ring of fentanyl skeleton reduced the potency and shortened the durati on of action of the parent compound, i.e., fentanyl. The antinociceptive po tency 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 agreem ent 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 interesti ng from the aspect of SAR studies and have potential promise for clinical a pplication, 3-carbomethoxy fentanyl deserves to be extensively evaluated.