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.