title: Antinociceptive profile of potent opioid peptide AM94, a fluorinated analogue of biphalin with non-hydrazine linker.
abstract: AM94 is a fluorinated analog of biphalin with non-hydrazine linker that has an in vitro affinity for μ-opioid and δ-opioid receptors tenfold higher than biphalin. Furthermore, in vivo evaluation in rats showed that AM94 has in hot plate test - after both intracerebroventricular and intravenous administrations - a greater and more durable efficacy than biphalin. Here, the antinociceptive profile of AM94 is further evaluated by following two different administration routes, intrathecal and subcutaneous, and two different animal species, rats and mice. The analgesic potency of AM94 is compared with that of both the parent peptide biphalin and morphine. Results show that in rats (tail flick test) and in mice (formalin test), AM94 has a higher and more durable analgesic effect than biphalin after intrathecal and subcutaneous administrations. Conformational properties of biphalin and AM94 were also investigated by variable-temperature (1)H NMR and energy minimization.
authors.affiliation: Dipartimento di Farmacia, Università di Chieti-Pescara G. d'Annunzio, Chieti, Italy. a.mollica@unich.it
authors.forename: Adriano
authors.initials: A
authors.lastname: Mollica
authors.forename: Roberto
authors.initials: R
authors.lastname: Costante
authors.forename: Azzurra
authors.initials: A
authors.lastname: Stefanucci
authors.forename: Francesco
authors.initials: F
authors.lastname: Pinnen
authors.forename: Gino
authors.initials: G
authors.lastname: Lucente
authors.forename: Stefano
authors.initials: S
authors.lastname: Fidanza
authors.forename: Stefano
authors.initials: S
authors.lastname: Pieretti
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D004745:Enkephalins / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000737:chemistry / Q000494:pharmacology; D018847:Opioid Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017433:Protein Structure, Secondary; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000737:chemistry / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000737:chemistry / Q000378:metabolism
chemical_list: D000700:Analgesics; D004745:Enkephalins; D018847:Opioid Peptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009020:Morphine; C053673:biphalin