ANTAGONISM OF GUT, BUT NOT CENTRAL EFFECTS OF MORPHINE WITH QUATERNARY NARCOTIC-ANTAGONISTS
ANTAGONISM OF GUT, BUT NOT CENTRAL EFFECTS OF MORPHINE WITH QUATERNARY NARCOTIC-ANTAGONISTS
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DOI：
10.1016/0014-2999(82)90026-7
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发表时间：
1982-01-01
影响因子：
5
通讯作者：
MERZ, H
中科院分区：
文献类型：
--
作者：
RUSSELL, J;BASS, P;MERZ, H
纳洛酮甲基溴化物和纳洛酮甲基溴化物，分别是纳洛酮和纳洛酮的四元衍生物，被认为是外周作用。这两种化合物都逆转了吗啡对狗肠道的刺激作用。甲基溴化纳洛酮5 mg/kg s.c.阻断吗啡诱导的肠峰电位50分钟，而静脉给药引起的拮抗作用仅为25分钟。途径与纳洛酮0.2 mg/kg s.c.产生的途径相似。在吗啡依赖的狗中，甲基溴化纳洛酮在0.25-50 mg/kg s.c.的剂量范围内似乎没有中枢拮抗吗啡。因为它不会引起麻醉剂戒断的行为迹象。静脉注射纳洛酮甲基溴化物也能够逆转吗啡诱导的狗的肠峰电位，但保护作用仅持续25分钟。在大鼠中，10和30 mg/kg静脉注射纳洛酮甲基溴化物既不能逆转PG[前列腺素] F2 α的吗啡阻断，也不能逆转PG[前列腺素] F2 α的吗啡阻断。诱导的腹泻，也没有抗伤害，这表明在两个测试中缺乏CNS麻醉剂拮抗作用。在小鼠中，口服60-720 mg/kg和腹膜内3-140 mg/kg的甲基溴化纳洛酮不能阻断吗啡对PG F 2 α的抑制。引起腹泻。特别是，在该物种中，30 mg/kg s.c.的甲基溴化纳洛酮似乎穿过血脑屏障，因为该剂量逆转了吗啡诱导的抗伤害感受。甲基溴化纳洛酮能有效地拮抗吗啡对狗的急性肠道刺激作用，但不能拮抗吗啡对狗的慢性行为作用。根据抗伤害试验，甲基溴化纳洛酮在大鼠中不能穿过血脑屏障，但在小鼠中可以。吗啡抑制PGF 2 α。在啮齿类动物中通过中枢机制诱发腹泻。
Naltrexone methylbromide and naloxone methylbromide, quaternary derivatives of naltrexone and naloxone, respectively, are assumed to act peripherally. Both compounds reversed the intestinal stimulating effect of morphine in the dog. Naltrexone methylbromide 5 mg/kg s.c. blocked morphine-induced intestinal spike potentials for 50 min while i.v. doses caused antagonism for only 25 min. The antagonism by the s.c. route approximated that produced by naltrexone 0.2 mg/kg s.c. In morphine-dependent dogs, naltrexone methylbromide did not appear to antagonize morphine centrally in doses ranging from 0.25-50 mg/kg s.c. since it did not induce behavioral signs of narcotic withdrawal. I.v. naloxone methylbromide was also able to reverse morphine-induced intestinal spike potential in dogs, but the protection lasted only 25 min. In rats, naltrexone methylbromide 10 and 30 mg/kg i.p. neither reversed morphine block of PG[prostaglandin]F2.alpha.-induced diarrhea nor antinociception, suggesting a lack of CNS narcotic antagonism in both tests. In mice, naltrexone methylbromide 60-720 mg/kg orally and 3-140 mg/kg i.p. failed to block morphine inhibition of PG F2.alpha.-induced diarrhea. Paradoxically, in this species, 30 mg/kg s.c. of naltrexone methylbromide appeared to cross the blood-brain barrier since this dose reversed morphine-induced antinociception. Naltrexone methylbromide effectively antagonizes the acute gut stimulating effect but not the chronic behavioral effect of morphine administration in dogs. Based upon the antinociception test, naltrexone methylbromide does not cross the blood-brain barrier in rats, but may in mice. Morphine inhibits PGF2.alpha.-induced diarrhea by a central mechanism in rodents.