Short-acting NMDA receptor antagonist MRZ 2/576 produces prolonged suppression of morphine withdrawal in mice.
The present study sought to evaluate the time-course of the effects of a short-acting glycine site NMDA receptor antagonist, MRZ 2/576 (half-life of about 20 min), on the expression of morphine withdrawal syndrome in mice. Morphine-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 injection. MRZ 2/576 suppressed expression of several signs of morphine withdrawal (jumping, shaking, forelimb tremor). Effects of MRZ 2/576 were equally expressed throughout 1-h observation test of both spontaneous and naltrexone-facilitated withdrawal. These results suggest that despite its short half-life, MRZ 2/576 produces prolonged suppression of morphine withdrawal syndrome and this effect cannot be attributed to repeated morphine-induced increase in sensitivity to naltrexone.
Belozertseva
I V
IV
Laboratory of Behavioral Pharmacology, Institute of Pharmacology, Pavlov Medical University, St. Petersburg, Russia.
Danysz
W
W
Bespalov
A Y
AY
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009020:Morphine / Q000009:adverse effects*; D009271:Naltrexone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use; D010793:Phthalazines / Q000627:therapeutic use*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*; D014202:Tremor / Q000188:drug therapy
C112266:MRZ 2-576; D009292:Narcotic Antagonists; D010793:Phthalazines; D016194:Receptors, N-Methyl-D-Aspartate; D009271:Naltrexone; D009020:Morphine