Unexpected and pronounced antinociceptive synergy between spinal acetaminophen (paracetamol) and phentolamine

Acetaminophen was administered to mice by spinal (intrathecal, i.t.) inject ion alone or with phentolamine (11.3 mug = 0.03 mu mol). Acetaminophen prod uced dose-related antinociception in the abdominal irritant test with an ED 50 value of 137.2 mug (0.9 mu mol). Phentolamine had no effect. For combine d administration, the potency of acetaminophen was significantly increased (ED50 = 24.4 vs. 137.2 mug), indicative of multiplicative interaction and s trong synergism. These results reveal the significant and surprising intera ction of spinal cord adrenoceptors or ion channel subtypes with acetaminoph en-induced antinociception. (C) 2001 Published by Elsevier Science B.V.