An antagonist of NR2B subunit-containing NMDA receptors
CP 101,606 is a noncompetitive antagonist of NMDA receptors containing the NR2B subunit (Kd = 4.2 nM).1 CP 101,606 is highly selective for NR1/NR2B-containing NMDA receptors over NR1, NR2A, and NR2B subunits alone and NR1/NR2A receptors in HEK293 cell homogenates. In vivo, CP 101,606 (30 mg/kg, s.c.) inhibits mechanical hyperalgesia following carrageenan challenge in rats.2 It also inhibits licking behavior in rats induced by capsaicin and phorbol-12-myristate-13-acetate . CP 101,606 reverses catalepsy in rats induced by haloperidol with an ED50 value of 0.4 mg/kg.3 CP 101,606 (1 mg/kg, s.c.) alone or in combination with L-DOPA methyl ester temporarily improves parkinsonian symptoms in an MPTP model of Parkinson's disease in rhesus monkeys.
1.Chazot, P.L., Lawrence, S., and Thompson, C.L.Studies on the subtype selectivity of CP-101,606: Evidence for two classes of NR2B-selective NMDA receptor antagonistsNeuropharmacology42(3)319-324(2002) 2.Taniguchi, K., Shinjo, K., Mizutani, M., et al.Antinociceptive activity of CP-101,606, an NMDA receptor NR2B subunit antagonistBr. J. Pharmacol.122(5)809-812(1997) 3.Steece-Collier, K., Chambers, L.K., Jaw-Tsai, S.S., et al.Antiparkinsonian actions of CP-101,606, an antagonist of NR2B subunit-containing N-methyl-d-aspartate receptorsExp. Neurol.163(1)239-243(2000)
Animal experiment: | Rats[3]The effect of traxoprodil and SPD on PTZ-induced seizures is investigated by injecting the Adult (90-100 days-old) male Wistar rats (250-300 g) with traxoprodil (0.2, 2 or 20 nM/site), SPD (0.02, 0.2 or 2 nM/site), or with vehicle (0.9% NaCl, 1 μL) 15 min before the administration of PTZ (35 or 70 mg/kg, i.p.)[3].Mice[2]The Forced swim test is done on male Albino Swiss mice (25-30 g). Traxoprodil (5, 10, 20, 40 mg/kg), imipramine and saline are administered i.p. 60 min before the test. The antidepressant activity is measured[2]. |
参考文献: [1]. Chenard BL, et al. (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol: a potent new neuroprotectant which blocks N-methyl-D-aspartate responses. J Med Chem. 1995 Aug 4;38(16):3138-45. | |
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