Antinociceptive activity of combination of morphine and NMDA receptor antagonists depends on the inter-injection interval.
Antinociceptive activity of combination of morphine and NMDA receptor antagonists depends on the inter-injection interval.
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吗啡和 NMDA 受体拮抗剂组合的镇痛活性取决于注射间隔。
DOI：
10.1016/s0014-2999(00)00184-9
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发表时间：
2000
影响因子：
5
通讯作者：
Bespalov,AY
中科院分区：
文献类型：
--
作者：
Belozertseva,IV;Dravolina,OA;Neznanova,ON;Danysz,W;Bespalov,AY
The actual time-course of morphine antinociception is shorter than what would be predicted from its elimination kinetics, suggesting the presence of an acute tolerance phenomenon. Since antagonists acting at NMDA subtype of glutamate receptors were repeatedly shown to prolong acute morphine antinociception, acute tolerance may be attributed to hyperactivity of NMDA receptors. The ability of various site-selective NMDA receptor antagonists to affect morphine antinociception (tail-flick test) was assessed in mice 30 and 120 min after acute morphine challenge. Competitive NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid (d-CPPene) (SDZ EAA 494; 0.1–1 mg/kg), low-affinity channel blockers 1-amino-3,5-dimethyl adamantane (memantine) (1–10 mg/kg) and 1-amino-1,3,3,5,5-pentamethyl-cyclohexan hydrochloride (MRZ 2/579) (1–10 mg/kg), glycine site antagonists 5-nitro-6,7-dichloro-1,4-dihydro-2,3-quinoxalinedione (ACEA-1021) (5 or 10 mg/kg) and 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridaliono(4,5-b)quinoline-5-oxide choline salt (MRZ 2/576) (1–10 mg/kg) were administered intraperitoneally (i.p.) 15 or 30 min prior to the tail-flick test (i.e., interval between injections of morphine and NMDA receptor antagonist was either 0–15 or 90–105 min). ACEA-1021, MRZ 2/576 and to the lesser extent, memantine and MRZ 2/579 enhanced morphine antinociception when tests were conducted 120 but not 30 min post-morphine. d-CPPene potentiated morphine antinociception irrespective of the interval between morphine administration and the tail-flick test. The results suggest that NMDA receptor antagonists may restore analgesic activity of morphine in acutely tolerant mice.
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