Further studies on arylpiperazinyl alkyl pyridazinones: discovery of an exceptionally potent, orally active, antinociceptive agent in thermally induce...
Basic Information
ID: ALA1154181
Journal: J Med Chem
Title: Further studies on arylpiperazinyl alkyl pyridazinones: discovery of an exceptionally potent, orally active, antinociceptive agent in thermally induced pain.
Authors: Biancalani C, Giovannoni MP, Pieretti S, Cesari N, Graziano A, Vergelli C, Cilibrizzi A, Di Gianuario A, Colucci M, Mangano G, Garrone B, Polenzani L, Dal Piaz V.
Abstract: A number of pyridazinone derivatives bearing an arylpiperazinylalkyl chain were synthesized and tested icv in a model of acute nociception induced by thermal stimuli in mice (tail flick). The most interesting and potent compound in this series was 6a, which showed an ED(50) = 3.5 microg, a value about 3-fold higher with respect to morphine by the same route of administration. When administered per os, 6a was 4-fold more potent than morphine in the same test, suggesting a significant bioavailability. The same compound also showed high potency in the hot plate test. The antinociceptive effect of 6a was completely reversed by pretreatment with yohimbine both in the hot plate test and in the tail flick test. This demonstrated the involvement of the adrenergic system, which was confirmed by in vitro radioligand binding studies.
CiteXplore: 19788200
DOI: 10.1021/jm900458r
Patent ID: ┄