氯丙嗪预处理对去肾上腺小鼠吗啡镇痛及纳洛酮效能的影响。

The effect of chlorpromazine pretreatment on morphine analgesia and naloxone potency in adrenalectomized mice.

Wong C L, Wai M K

Clin Exp Pharmacol Physiol. 1982 Nov-Dec;9(6):595-601. doi: 10.1111/j.1440-1681.1982.tb00830.x.

Abstract

Morphine pretreatment (2.0 mg/kg s.c.) induced no overt tolerance to its antinociceptive effect in mice 3 h later, but enhanced the antagonistic potency of naloxone. 2. Pretreatment with chlorpromazine slightly potentiated the antinociceptive effect of morphine measured 3.5 h later. The antagonistic effect of naloxone was also enhanced. 3. The observed effect of chlorpromazine on naloxone potency was augmented when naloxone was administered in the pretreatment regime. 4. The enhanced naloxone potency induced by morphine pretreatment was inhibited by chlorpromazine administered 0.5 h before the morphine pretreatment. 5. Adrenalectomy sensitized the animals to the antinociceptive effect of morphine. However, the naloxone potency was similar to that of the sham-operated controls. 6. Adrenalectomy greatly attenuated the effect of chlorpromazine pretreatment on naloxone potency. However, the effect of combined pretreatment with either chlorpromazine plus naloxone or morphine remained unaffected. 7. These results indicate that the increased naloxone potency after chlorpromazine pretreatment may be partly mediated through an adrenal-linked process. However, it appears that this process is not essential for the development of increased naloxone potency induced by morphine pretreatment and for the interaction between chlorpromazine, naloxone and morphine.

摘要

吗啡预处理（2.0毫克/千克，皮下注射）3小时后未诱导小鼠对其镇痛作用产生明显耐受性，但增强了纳洛酮的拮抗效力。2. 氯丙嗪预处理使3.5小时后测得的吗啡镇痛作用略有增强。纳洛酮的拮抗作用也增强。3. 当纳洛酮在预处理阶段给药时，氯丙嗪对纳洛酮效力的观察效应增强。4. 在吗啡预处理前0.5小时给予氯丙嗪可抑制吗啡预处理诱导的纳洛酮效力增强。5. 肾上腺切除使动物对吗啡的镇痛作用敏感。然而，纳洛酮效力与假手术对照组相似。6. 肾上腺切除大大减弱了氯丙嗪预处理对纳洛酮效力的影响。然而，氯丙嗪加纳洛酮或吗啡联合预处理的效果不受影响。7. 这些结果表明，氯丙嗪预处理后纳洛酮效力增加可能部分通过肾上腺相关过程介导。然而，似乎该过程对于吗啡预处理诱导的纳洛酮效力增加以及氯丙嗪、纳洛酮和吗啡之间的相互作用的发展并非必不可少。