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

The Japanese Journal of Pharmacology

Milovan Ivanovic²  Radan Stojanovic³  Sonja Vuckovic³  Milica Prostran³  Zorana Ristovic¹ 

[1] Institute of Oncology and Radiology,Pasterova 14,11000 Belgrade,Yugoslavia;Faculty of Chemistry,University of Belgrade,Studentski trg 12-16,P.O.Box 158,11001 Belgrade,Yugoslavia;Department of Clinical Pharmacology,Pharmacology and Toxicology,School of Medicine,University of Belgrade,Dr Suboti'ca 1,P.O.Box 840,11129 Belgrade,Yugoslavia

关键词: Antinociception;    Fentanyl;    Carfentanil;    Structure-activity-relationship;   

DOI  :  10.1254/jjp.84.188

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(40)Cited-By(5)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.

【 授权许可】

Unknown