Further studies on arylpiperazinyl alkyl pyridazinones: discovery of an exceptionally potent, orally active, antinociceptive agent in thermally induced pain.

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.

DOI: 10.1021/jm900458r
050100150201520162017
Citations per Year

Citation Velocity: 17

Averaging 17 citations per year over the last 3 years.

Learn more about how we calculate this metric in our FAQ.