Behavioural effects of the novel AMPA/GluR5 selective receptor antagonist NS1209 after systemic administration in animal models of experimental pain.
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.
Department of Pharmacology, NeuroSearch A/S, Pederstrupvej 93, DK-2750 Ballerup, Denmark. gbm@neurosearch.dk
Gordon
G
Blackburn-Munro
Signe F
SF
Bomholt
Helle K
HK
Erichsen
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D008297:Male; D009020:Morphine / Q000627:therapeutic use; D009294:Narcotics / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D011758:Pyrroles / Q000627:therapeutic use*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors*; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D009020:Morphine; D009294:Narcotics; D011758:Pyrroles; D011810:Quinoxalines; D018092:Kainic Acid Receptors; D044005:Tetrahydroisoquinolines; C119326:SPD 502; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline