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

Abstract

1 Non-steroidal anti-in¯ammatory drugs (NSAIDs) are e ective anti-in¯ammatory and analgesic drugs although they also induce unwanted side e ects due to the inhibition of the physiological e ects regulated by prostaglandins. This has led to the search for new compounds with fewer side e ects, such as the nitro-NSAIDs (NO-NSAIDs). Paracetamol is an analgesic drug devoid of some of the side e ect of the NSAIDs but without anti-in¯ammatory activity. NCX-701 is a nitric oxide releasing version of paracetamol with anti-in¯ammatory 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 e ects in responses to noxious mechanical and electrical stimulation (wind-up). 3 Paracetamol did not induce any signi®cant e ect at the doses tested (maximum of 480 mmol kg 71 , 72.5 mg kg 71 ). NCX-701 however was very e ective in reducing responses to noxious mechanical stimulation (32+10% of control response) and wind-up (ED 50 of 147+1 mmol kg 71 , 41.5+0.3 mg kg 71 ). The inhibition was not reversed by 1 mg kg 71 of the opioid antagonist naloxone. In control experiments performed with either the vehicle or the NO donor NOC-18, no signi®cant changes were observed in the nociceptive responses studied. 4 We conclude that NCX-701 is a very e ective non-opioid antinociceptive agent in normal animals and its action is located mainly at central areas. The antinociceptive e ect was not due solely to the release of NO.

Enhancement of fentanyl antinociception by subeffective doses of nitroparacetamol (NCX-701) in acute nociception and in carrageenan-induced monoarthritis

“…For NCX-701, the dose was less than half of that observed to be effective in preliminary experiments, and even lower than the minimum effective dose observed after i.v. administration in electrophysiological experiments (Romero-Sandoval et al, 2002). This suggests that the interaction occurred within the subanalgesic dose range, supporting the results observed in electrophysiological experiments.…”

The antinociceptive effect of systemic gabapentin is related to the type of sensitization-induced hyperalgesia

“…The experiments are performed in a less traumatic preparation than that needed in other techniques which, for example, require laminectomy and full exposition of the spinal cord, avoiding artificial and extra nociceptive inputs. The experiments are, in this case, carried out in a much more similar conditions and data are very reproducible [27,29,38-40]. …”

The oral administration of retinoic acid enhances nociceptive withdrawal reflexes in rats with soft-tissue inflammation

“…Some studies, for example, have shown a clear relationship between retinoic acid and the generation of nitric oxide (NO) [9,12,28], prostaglandins [4,11] and the expression of cyclooxigenase 1 (COX-1) [23] and COX-2 [14,17]. All these mediators are involved in the generation or maintenance of sensitization and pain due to inflammation and are the targets for many painkillers studied in our lab among many others [7,10,26].…”