TY - JOUR T1 - Antinociceptive Activity of the <em>N</em>-Methyl-<span class="sc">d</span>-aspartate Receptor Antagonist <em>N</em>-(2-Indanyl)-glycinamide Hydrochloride (CHF3381) in Experimental Models of Inflammatory and Neuropathic Pain JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 804 LP - 814 DO - 10.1124/jpet.103.050039 VL - 306 IS - 2 AU - Gino Villetti AU - Marco Bergamaschi AU - Franco Bassani AU - Pier Tonino Bolzoni AU - Marisa Maiorino AU - Claudio Pietra AU - Ivano Rondelli AU - Philippe Chamiot-Clerc AU - Michele Simonato AU - Mario Barbieri Y1 - 2003/08/01 UR - http://jpet.aspetjournals.org/content/306/2/804.abstract N2 - N-(2-Indanyl)-glycinamide hydrochloride (CHF3381) is a novel low-affinity, noncompetitive N-methyl-d-aspartate receptor antagonist. The current study compared the antinociceptive effects of CHF3381 with those of gabapentin and memantine in in vitro and in vivo models of pain. In isolated rat spinal cord, CHF3381 and memantine, but not gabapentin, produced similar inhibition of the wind-up phenomenon. CHF3381 suppressed the maintenance of carrageenan-induced thermal and mechanical hyperalgesia in the rat with a minimum significantly effective dose (MED) of 30 mg/kg p.o. Memantine produced a partial reversal of both thermal and mechanical hyperalgesia (MED = 10 and 15 mg/kg i.p., respectively). Gabapentin reversed mechanical hyperalgesia (MED = 10 mg/kg s.c.), but did not affect thermal hyperalgesia. In the mouse formalin test, CHF3381 and memantine preferentially inhibited the late phase (MED = 30 and 20 mg/kg i.p., respectively); gabapentin inhibited only the late phase (MED = 30 mg/kg s.c.). Unlike morphine, CHF3381 chronic administration was not accompanied by the development of tolerance in the formalin test. Furthermore, morphine tolerance did not cross-generalize to CHF3381. In rats with a sciatic nerve injury, CHF3381 relieved both cold and mechanical allodynia (MED = 100 mg/kg p.o.). In contrast, memantine was inactive. Gabapentin blocked cold allodynia (MED = 30 mg/kg s.c.), but had marginal effects on mechanical allodynia. In diabetic neuropathy, CHF3381 reversed mechanical hyperalgesia (MED = 50 mg/kg p.o.). Memantine (15 mg/kg i.p.) produced an antinociceptive effect, whereas gabapentin (100 mg/kg p.o.) had no significant effect. Thus, CHF3381 may be useful for the therapy of peripheral painful neuropathies. The American Society for Pharmacology and Experimental Therapeutics ER -