GV-196771A是GV196771的钠盐形式。是NMDA受体拮抗剂。
GV-196771A is the sodium salt form of GV196771, is an NMDA receptor antagonist.
GV196771 is a potent antagonist of the modulatory glycine site of the N-methyl-D-aspartate receptor. GV196771 is a potent antagonist of the modulatory glycine site of the NMDA receptor developed for treatment of neuropathic pain. GV196771 is an NMDA receptor antagonist with low oral bioavailability in rats and mice. GV196771 has low oral bioavailability (<10%) and plasma clearance (~2 mL/min/kg) in rats[1].
[1]. Polli JW, et al. The systemic exposure of an N-methyl-D-aspartate receptor antagonist is limited in mice by the P-glycoprotein and breast cancer resistance protein efflux transporters. Drug Metab Dispos. 2004 Jul;32(7):722-6.
Animal experiment: | Mice[1] Male wild-type FVB mdr1a/1b+/+ and Pgp-deficient knockout FVBmdr1a/1b-/- mice (20-30 g) are used. Dose solutions of 0.2 mg/mL for GV196771 and 5.0 mg/mL for GF120918 are prepared fresh using 0.5% hydroxypropylmethylcellulose and 1% Tween 80 as a vehicle. Two hours before the administration of GV196771, the animals are divided into two groups. One group receive a single oral dose (10 mL/kg) of vehicle and the second group receive a single 50 mg/kg oral dose (10 mL/kg) of GF120918. Two hours later, all animals receive a single 2 mg/kg oral dose (10 mL/kg) of GV196771. At scheduled time points, mice are anesthetized with CO2 and blood samples are obtained by cardiac puncture. Blood is centrifuged to yield plasma. The MDR genotype of each animal is confirmed by a polymerase chain reaction assay after study completion. |
参考文献: [1]. Polli JW, et al. The systemic exposure of an N-methyl-D-aspartate receptor antagonist is limited in mice by the P-glycoprotein and breast cancer resistance protein efflux transporters. Drug Metab Dispos. 2004 Jul;32(7):722-6. | |
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