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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Synthesis and analgesic effects of 3-substituted 4,6-diarylpyridazine derivatives of the arylpiperazine class.

A new series of 4,6-diaryl pyridazines substituted in the 3-position by arylpiperazinyl moieties was synthesized and evaluated for analgesic activity. Five out of the nine tested compounds possessed significant antinociceptive effects in the phenylbenzoquinone-induced writhing test (PBQ test) with ED50 values ranging from 26.0 to 37.7 mg/kg ip. The most active derivatives 2a, 2d and 2h had a low toxicity (LD50 > 800 mg/kg ip) but showed some sedative and neurotoxic effects from the dose of 50 mg/kg ip. The three selected pyridazines were devoid of activity in the hot-plate test. However, analgesic activity of 2d and 2h was significantly reversed by naloxone in the PBQ test. Administered at the low dose of 5 mg/kg ip, 2h greatly potentiated the antinociceptive response induced by morphine (0.15 mg/kg sc). In addition, analgesic effects of 2h (2.5 mg/kg ip) were also potentiated by 5-hydroxytryptophan combined with carbidopa. These results suggest that pyridazine 2h induces analgesia, which is mediated via both opioid and serotonergic mechanisms.[1]

References

  1. Synthesis and analgesic effects of 3-substituted 4,6-diarylpyridazine derivatives of the arylpiperazine class. Rohet, F., Rubat, C., Coudert, P., Couquelet, J. Bioorg. Med. Chem. (1997) [Pubmed]
 
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