Iv. Belozertseva et al., Short-acting NMDA receptor antagonist MRZ 2/576 produces prolonged suppression of morphine withdrawal in mice, N-S ARCH PH, 361(3), 2000, pp. 279-282
The present study sought to evaluate the timecourse of the effects of a sho
rt-acting glycine site NMDA receptor antagonist, MRZ 2/576 (half-life of ab
out 20 min), on the expression of morphine withdrawal syndrome in mice. Mor
phine-naive and morphine-dependent mice (10-100 mg/kg, b.i.d., s.c., 9 days
) were injected with a combination of naltrexone (vehicle or 1 mg/kg, s.c.)
and MRZ 2/576 (vehicle, 0.3-10 mg/kg, i.p.) 24 h after the last morphine i
njection. MRZ 2/576 suppressed expression of several signs of morphine with
drawal (jumping, shaking, forelimb tremor). Effects of MRZ 2/576 were equal
ly expressed throughout 1-h observation test of both spontaneous and naltre
xone-facilitated withdrawal. These results suggest that despite its short h
alf-life, MRZ 2/576 produces prolonged suppression of morphine withdrawal s
yndrome and this effect cannot be attributed to repeated morphine-induced i
ncrease in sensitivity to naltrexone.