Behavioural effects of the novel AMPA/GluR5 selective receptor antagonist NS1209 after systemic administration in animal models of experimental pain

• Published in: Neuropharmacology 2004-09, Vol.47 (3), p.351-362
• Main Authors: Blackburn-Munro, Gordon, Bomholt, Signe F, Erichsen, Helle K
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Central sensitisation; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Routes; Excitatory Amino Acid Antagonists - therapeutic use; Glutamate; Kainate receptor; Male; Morphine - therapeutic use; Narcotics - therapeutic use; Neuropathic pain; Pain - drug therapy; Pain Measurement - drug effects; Pain Measurement - methods; Pain Threshold - drug effects; Peripheral Nervous System Diseases - drug therapy; Pyrroles - therapeutic use; Quinoxalines - pharmacology; Rat formalin test; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Receptors, Kainic Acid - antagonists & inhibitors; Rodentia; Tail flick test; Tetrahydroisoquinolines - therapeutic use; Time Factors
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2004.04.007

The effects of systemic administration of the novel AMPA/GluR5 selective receptor antagonist NS1209 in animal models of experimental pain have been tested and compared with the AMPA receptor antagonist NBQX and the opiate morphine. In the mouse hot plate test, NS1209 (3–30 mg/kg, s.c. and i.p.) and morphine (3–30 mg/kg, s.c.) significantly increased the nociceptive response latency, whereas NBQX (3–30 mg/kg, i.p.) was ineffective. In the rat formalin test, a model of persistent pain, NS1209 (3 and 6 mg/kg, i.p.) and morphine (0.5 and 3 mg/kg, s.c.) produced dose-dependent reductions in second phase nociceptive behaviours, although NBQX (10 and 20 mg/kg, i.p.) was without effect. In the chronic constriction injury model of neuropathic pain, NS1209 (3 and 6 mg/kg, i.p.), NBQX (10 and 20 mg/kg, i.p.) and morphine (3 and 6 mg/kg, s.c.) all reduced mechanical allodynia and hyperalgesia responses to von Frey hair and pin prick stimulation of the injured hindpaw. NS1209 and morphine also reduced cold hypersensitivity in response to ethyl chloride stimulation of the injured hindpaw. At the doses associated with anti-nociceptive actions, no effects on motor performance as determined by the rotarod test were observed for any of the drugs tested. Thus, systemic administration of NS1209 at non-ataxic doses has marked analgesic actions comparable to those of morphine in a range of animal models of experimental pain.