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.

Antinociceptive profile of potent opioid peptide AM94, a fluorinated analogue of biphalin with non-hydrazine linker

MOLLICA, ADRIANO;COSTANTE, ROBERTO;STEFANUCCI, AZZURRA;PINNEN, Francesco Enrico;
2013-01-01

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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/656687
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 27
  • ???jsp.display-item.citation.isi??? 23
social impact