title: Synthesis and opioid activity of new fentanyl analogs.
abstract: Three new fentanyl analogs (compounds 3-4-5) have been synthesized and evaluated for antinociceptive properties using the writhing test. The analgesic property of the active compound, N-[1-phenylpyrazol-3-yl]-N-[1-(2-phenethyl)-4-piperidyl)] propenamide (compound 4), was tested using the hot plate test in mice. Its opioid agonistic activity was characterized using three isolated tissues: guinea pig ileum, mouse vas deferens, and rabbit vas deferens. Compound 4 was as effective as fentanyl or morphine and it showed less antinociceptive potency than fentanyl but it was more potent than morphine. The duration of the antinociception was similar to that of fentanyl. This compound inhibited the electrically evoked contractions of myenteric plexus-longitudinal muscle strips of guinea pig ileum and of mouse vas deferens but not those of rabbit vas deferens. These effects could be reversed by micro selective antagonists (naloxone and/or CTOP) but not by the delta selective antagonist naltrindole, thus indicating that the compound acted as a micro opioid agonist. Finally, the binding data confirmed that compound 4 had high affinity and selectivity for the micro-receptor.
authors.affiliation: Unidad de Farmacología, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Avda. Atenas, s/n, E-28922 Alcorcón, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Girón
authors.forename: Raquel
authors.initials: R
authors.lastname: Abalo
authors.forename: Carlos
authors.initials: C
authors.lastname: Goicoechea
authors.forename: Ma Isabel
authors.initials: MI
authors.lastname: Martín
authors.forename: Luis F
authors.initials: LF
authors.lastname: Callado
authors.forename: Carolina
authors.initials: C
authors.lastname: Cano
authors.forename: Pilar
authors.initials: P
authors.lastname: Goya
authors.forename: Nadine
authors.initials: N
authors.lastname: Jagerovic
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D011817:Rabbits; D017450:Receptors, Opioid, mu / Q000187:drug effects; D013045:Species Specificity; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D005283:Fentanyl