Subeffective doses of nitroparacetamol (NCX-701) enhance the antinociceptive activity of the α₂-adrenoceptor agonist medetomidine

Pharmacol Biochem Behav. 2011 Sep;99(3):385-90. doi: 10.1016/j.pbb.2011.05.022. Epub 2011 May 27.

Abstract

The α₂-adrenergic system is involved in pain processing and inflammation-induced sensitization. α₂-adrenoceptor agonists induce analgesia, and this effect is greater when administered in combination with other analgesics. In the present study, we assessed a possible enhancement of antinociception combining the α₂-adrenoceptor agonist medetomidine with subeffective doses of NCX701 (nitroparacetamol). The effects of the drugs were studied in spinal cord neuronal responses from adult male Wistar rats with carrageenan-induced inflammation, using the recording of single motor unit technique. The experiments showed that the i.v. administration of medetomidine and NCX701 induced a more potent and effective antinociceptive effect than medetomidine when given alone (ID₅₀: 0.47±0.1 vs. 1.1±0.1 μg/kg) or in the presence of paracetamol, in naturally-evoked nociceptive responses. In addition, the duration of antinociception was significantly longer (P<0.001, 100 min after administration). The use of low doses of NCX701 and α₂-adrenoceptor agonists might open new perspectives in the treatment of inflammatory pain.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / analogs & derivatives*
  • Adrenergic alpha-2 Receptor Agonists / administration & dosage*
  • Analgesics, Non-Narcotic / administration & dosage*
  • Animals
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Male
  • Medetomidine / administration & dosage*
  • Nitrates / administration & dosage*
  • Pain Measurement / drug effects*
  • Pain Measurement / methods
  • Rats
  • Rats, Wistar

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Analgesics, Non-Narcotic
  • Nitrates
  • Acetaminophen
  • 4-(nitroxy)butanoic acid 4-acetylaminophenyl ester
  • Medetomidine