Effects of intracerebroventricularly administered chimeric peptide of Metenkephalin and FMRFa-[D-Ala(2)]YFa-on antinociception and its modulation in mice

An enzymatically stable analog of YGGFMKKKFMR-Famide (YFa), a chimeric pept ide of metenkephalin and FMRFa, was synthesised. The antinociceptive effect s of intracerebroventricular injections of this analog - [D-Ala(2)]YAGFMKKK FMRFamide ([D-Ala(2)]YFa)-was then investigated using the mouse radiant-hea t tail-flick test. [D-Ala(2)]YFa produced modest to good antinociception at 1, 2, and 5 mug/mouse (0.64, 1,28, and 3.22 nmol, respectively). This anti nociceptive effect was completely reversed by the opioid receptor antagonis t naloxone (1.5 mug/mouse: 4.12 nmol, intracerebroventricular [i.c.v.]), ad ministered 5 min prior. Pretreatment (5 min) with either neuropeptides FF ( 1 mug/mouse: 0.92 nmol, i.c.v.) or FMRFa (1 mug/mouse: 1.69 nmol, i.c.v.) s ignificantly attenuated the antinociceptive effects induced by [D-Ala(2)]YF a (1 mug/mouse, i.c.v.), Intracerebroventricular administration of [D-Ala(2 )]YFa at 1 mug/mouse dose with morphine (2 mug/mouse: 5.86 nmol, i.c.v,) pr oduced an additive antinociceptive effect, suggesting that [D-Ala(2)]YFa ma y have a modulatory effect on opioid (morphine) analgesia. These results pr ovide further support for a role of such amphiactive sequences in antinocic eption and its modulation. (C) 2001 Elsevier Science Inc.