Pharmacology of cizolirtine: A new analgesic agent

Cizolirtine citrate (E-4018) is a new analgesic agent with antinociceptive activity against phenylquinone (ED50 33.7 mg/kg) and acetic acid (ED50 24.4 mg/kg) in mice, against acetic acid in rats (ED50 21.3 mg/kg) and in the p lantar test (ED50 26.8 mg/kg). It demonstrated antinociceptive activity in the mil-pinch and rail-Slick tests (ED(50)s of 68.0 and 46.0 mg/kg, respect ively), in both phases of the formalin lest (ED50 13.8 and 2.31 mg/kg), and in the capsaicin rest (ED50 7.14 mg/kg). Cizolirtine does not inhibit pros taglandin biosynthesis, it is not a ligand for opioid receptors, it does no t have antiinflammatory or ulcerogenic activity ii has some antipyretic act ivity and shows no affinity for alpha(2)-adrenergic receptors, but its anal gesic effect Mas modified by idazoxan and by desipramine. Recent studies ha ve shown that the analgesic effect of cizolirtine could be related at least partially, to an inhibition of spinal substance P release. (C)2000 Prous S cience. All rights reserved.