NCX-701 (nitroparacetamol) is an effective antinociceptive agent in rat withdrawal reflexes and wind-up

1. Non-steroidal anti-inflammatory drugs (NSAIDs) are effective anti-inflammatory and analgesic drugs although they also induce unwanted side effects due to the inhibition of the physiological effects regulated by prostaglandins. This has led to the search for new compounds with fewer side effects, such as the nitro-NSAIDs (NO-NSAIDs). Paracetamol is an analgesic drug devoid of some of the side effect of the NSAIDs but without anti-inflammatory activity. NCX-701 is a nitric oxide releasing version of paracetamol with anti-inflammatory and analgesic properties. 2. We have tested, in the single motor unit technique, the antinociceptive actions of intravenous cumulative doses of NCX-701 vs paracetamol, studying their antinociceptive effects in responses to noxious mechanical and electrical stimulation (wind-up). 3. Paracetamol did not induce any significant effect at the doses tested (maximum of 480 micromol kg(-1), 72.5 mg kg(-1)). NCX-701 however was very effective in reducing responses to noxious mechanical stimulation (32+/-10% of control response) and wind-up (ED(50) of 147+/-1 micromol kg(-1), 41.5+/-0.3 mg kg(-1)). The inhibition was not reversed by 1 mg kg(-1) of the opioid antagonist naloxone. In control experiments performed with either the vehicle or the NO donor NOC-18, no significant changes were observed in the nociceptive responses studied. 4. We conclude that NCX-701 is a very effective non-opioid antinociceptive agent in normal animals and its action is located mainly at central areas. The antinociceptive effect was not due solely to the release of NO.