1-Aminocyclopropane carboxylic acid (ACPC) prevents mu and delta opioid tolerance.
1-Aminocyclopropane carboxylic acid (ACPC) prevents mu and delta opioid tolerance.
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DOI：
10.1016/0024-3205(94)00753-5
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发表时间：
1994
期刊：
影响因子：
6.1
通讯作者：
Y. Kolesnikov;Maria-Luisa Maccechini;G. Pasternak;G. Pasternak
中科院分区：
文献类型：
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作者：
Y. Kolesnikov;Maria-Luisa Maccechini;G. Pasternak;G. Pasternak
1-氨基环丙烷羧酸(ACPC)是NMDA受体甘氨酸位置的部分激动剂，当与阿片类药物联合给药时，可防止对Mu阿片类吗啡和增量配体[D-Pen2，D-Pen5]脑啡肽(DPDPE)的耐受。相反，ACPC并不显著影响对kappa1阿片类药物U50,488H或kappa3配体纳洛酮苯甲酰肼(NalBzH)的耐受性。ACPC的行动仅限于宽容。单独给药时，ACPC在甩尾试验中没有镇痛作用，也不会改变幼鼠体内吗啡的ED50。单独长期给药5天不影响小鼠对吗啡的敏感性。ACPC还会反转先前存在的公差。当小鼠对吗啡耐受超过5天，然后与吗啡一起服用ACPC时，尽管继续注射吗啡，但3天内止痛恢复到朴素水平。ACPC对阿片类药物耐受性的作用与先前报道的竞争性和非竞争性NMDA拮抗剂的作用非常一致。
1-Aminocyclopropane carboxylic acid (ACPC), a partial agonist of the glycine site of the NMDA receptor, prevents tolerance to the mu opioid morphine and the delta ligand [D-Pen2,D-Pen5]enkephalin (DPDPE) when co-administered with the opioid. In contrast, ACPC does not significantly influence tolerance to the kappa1opioid U50,488H or the kappa3ligand naloxone benzoylhydrazone (NalBzH). The actions of ACPC are restricted to tolerance. When given alone, ACPC has no analgesic actions in the tailflick assay and it does not change morphine's ED50in naive mice. Chronic administration of ACPC alone for 5 days does not affect the sensitivity of mice to morphine. ACPC also reverses preexisting tolerance. When mice are made tolerant to morphine over 5 days and then receive ACPC along with their morphine, analgesia returns to naive levels within 3 days despite the continued administration of morphine. The actions of ACPC on opioid tolerance correspond closely with those previously described with both competitive and non-competitive NMDA antagonists.