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

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.

• Authors: Carlos Molina, Juan F Herrero
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 99 Issue 3 Pg. 385-90 (Sep 2011) ISSN: 1873-5177 [Electronic] United States
• PMID: 21640748 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• Acetaminophen (administration & dosage, 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, methods)
• Rats
• Rats, Wistar