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急性吗啡化大鼠和小鼠中戒断反应的诱发与预防:纳洛酮、纳曲酮和二丙诺啡之间的比较(作者译)

[Precipitation and prevention of abstinence in acutely morphinized rats and mice: comparisons between naloxone, naltrexone, and diprenorphine (author's transl)].

作者信息

Tremblay E, Colombel M C, Jacob J

出版信息

Psychopharmacology (Berl). 1976 Aug 26;49(1):41-8.

PMID:822446
Abstract

Abstinence signs were precipitated in rats by naloxone (1 mg - kg-1 s.c.) injected at various times (from 1.5 to 16 h) after a single dose of morphine hydrochloride (15 or 50 mg - kg-1 s.c.) administered in aqueous solution. Increasing the dose of morphine increased the latency of the phenomena and the duration of the underlying state; "shifts" of signs as described by Bläsig et al. (1974) in chronically morphinized rats also occurred when increasing the dose of morphine and the time interval between the injections of morphine and of naloxone. Naltrexone and diprenorphine were also effective. These three antagonists, given before morphine, were able to prevent precipitated abstinence: however, naloxone was almost ineffective when the higher dose of morphine was used and when the time interval was long. In these latter conditions, naltrexone was definitely more effective and longer acting and diprenorphine still more so. The same characteristics were found for the protective action of the three antagonists in acutely morphinized mice and the same order for their potencies in precipitating abstinence in acutely morphinized mice. Like naloxone, naltrexone and diprenorphine facilitated a nociceptive reaction in normal mice. The abstinence signs precipitated in acutely morphinized rats or mice are probably not unmasked excitatory effects of morphine as such effects should have been increased rather than inhibited by previous administration of specific antagonists; they might correspond to potentiated effects of the antagonists themselves. The prevention by specific antagonists of the abstinence syndrome is most simply interpreted by antagonism (direct or indirect) of dependence induction, but other interpretations are not excluded.

摘要

在大鼠单次皮下注射盐酸吗啡(15或50mg·kg⁻¹)的水溶液后,于不同时间(1.5至16小时)皮下注射纳洛酮(1mg·kg⁻¹)可引发戒断体征。增加吗啡剂量会延长这些现象的潜伏期以及基础状态的持续时间;当增加吗啡剂量以及吗啡与纳洛酮注射之间的时间间隔时,也会出现如Bläsig等人(1974年)所描述的慢性吗啡依赖大鼠中的体征“转变”。纳曲酮和二丙诺啡也有效。这三种拮抗剂在吗啡之前给药能够预防诱发的戒断反应:然而,当使用较高剂量的吗啡且时间间隔较长时,纳洛酮几乎无效。在这些情况下,纳曲酮肯定更有效且作用时间更长,而二丙诺啡则更甚。在急性吗啡依赖的小鼠中,这三种拮抗剂的保护作用也呈现相同特征,并且它们在急性吗啡依赖小鼠中诱发戒断反应的效力顺序相同。与纳洛酮一样,纳曲酮和二丙诺啡会促进正常小鼠的伤害性反应。在急性吗啡依赖的大鼠或小鼠中诱发的戒断体征可能并非吗啡本身未被掩盖的兴奋作用,因为此类作用本应因先前给予特异性拮抗剂而增强而非受到抑制;它们可能对应于拮抗剂自身的增强作用。特异性拮抗剂对戒断综合征的预防作用最简单的解释是对依赖诱导的拮抗作用(直接或间接),但其他解释也并非不可能。

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引用本文的文献

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Br J Pharmacol. 1978 Sep;64(1):91-8. doi: 10.1111/j.1476-5381.1978.tb08645.x.
2
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Br J Clin Pharmacol. 1979;7 Suppl 3(Suppl 3):291S-296S. doi: 10.1111/j.1365-2125.1979.tb04703.x.
3
[Comparisons between the effects of apomorphine and naloxone in acutely dependent morphinized rats and mice (author's transl)].阿扑吗啡与纳洛酮对急性吗啡依赖大鼠和小鼠作用的比较(作者译)

本文引用的文献

1
A critique of the "dual action" hypothesis of morphine physical dependence.对吗啡身体依赖性“双重作用”假说的批判。
Arch Int Pharmacodyn Ther. 1962 Dec 1;140:514-20.
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Demonstration of tolerance and physical dependence in the dog following a short-term infusion of morphine.短期输注吗啡后犬的耐受性和身体依赖性的表现。
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Effects of single doses of N-Allylnormorphine on hindlimb reflexes of chronic spinal dogs during cycles of morphine addiction.
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Naloxone-precipitated jumping activity in mice following the acute administration of morphine.急性给予吗啡后小鼠体内纳洛酮诱发的跳跃活动。
Eur J Pharmacol. 1974 Apr;26(1):122-4. doi: 10.1016/0014-2999(74)90084-3.
7
[Enhancement of nociceptive reactions by naloxone in mice and rats (author's transl)].纳洛酮对小鼠和大鼠伤害性反应的增强作用(作者译)
Psychopharmacologia. 1974 Jul 11;37(3):217-23. doi: 10.1007/BF00421535.
8
Potential usefulness of single-dose acute physical dependence on and tolerance to morphine for the evaluation of narcotic antagonists.单剂量急性吗啡身体依赖性和耐受性在麻醉性拮抗剂评价中的潜在用途。
Adv Biochem Psychopharmacol. 1973;8(0):299-318.
9
Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats.大鼠对吗啡身体依赖性的发展与时间、剂量的关系以及戒断综合征的量化
Psychopharmacologia. 1973 Oct 23;33(1):19-38. doi: 10.1007/BF00428791.
10
Failure of naloxone to prevent acute morphine tolerance and dependence.纳洛酮未能预防急性吗啡耐受性和依赖性。
Arch Int Pharmacodyn Ther. 1974 Sep;211(1):58-63.