(+)-HA 966, a partial agonist at the glycine site coupled to NMDA receptors, blocks formalin-induced pain in mice.
(+)-(1-Hydroxy-3-aminopyrrolidine-2-one) ((+)-HA 966), a partial agonist at the glycine site coupled to N-methyl-D-aspartic acid (NMDA) receptors, abolished the late phase of licking induced by injection of formalin into the hind-paw of mice; inhibitory dose50 (ID50) = 1.6 mg/kg, s.c. In contrast, it was weakly active against the first phase; ID50 = 33.3 mg/kg, s.c. Further, (+)-HA 966 was inactive in the rotarod test of ataxia. These data support a role of NMDA receptors in the transmission of prolonged noxious stimulation and suggest that partial glycine receptor agonists may exert antinociceptive properties against persistent pain.
Millan
M J
MJ
Institut de Recherches Servier, Puteaux, France.
Seguin
L
L
D000818:Animals; D005557:Formaldehyde / Q000633:toxicity; D005998:Glycine / Q000378:metabolism*; D006614:Hindlimb; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D011760:Pyrrolidinones / Q000494:pharmacology* / Q000627:therapeutic use; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism
D011760:Pyrrolidinones; D016194:Receptors, N-Methyl-D-Aspartate; D005557:Formaldehyde; C001369:1-hydroxy-3-amino-2-pyrrolidone; D005998:Glycine