Paracetamol inhibits nitric oxide synthesis in murine spinal cord slices

Paracetamol is an effective analgesic but its mechanism of action is unclear. We investigated the effect of paracetamol and the analgesic adjuvant caffeine on the activity of NO synthase in mouse spinal cord and cerebellar slices in vitro, by measuring the conversion of [3H]arginine to [3H]citrulline. Paracetamol (100 μM) had no effect on NO synthase activity in cerebellum, but in the spinal cord both paracetamol (100 μM) and caffeine (30 μM) attenuated glutamate (5 mM)-induced [3H]citrulline production and in combination they abolished it. In conclusion paracetamol inhibits spinal cord NO synthesis and this may be related to its analgesic effects.