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纳洛酮对小脑环磷酸鸟苷含量的影响。一种可能的γ-氨基丁酸拮抗作用?

The effect of naloxone on cerebellar cGMP content. A possible GABA-antagonistic action?

作者信息

Gumulka S W, Dinnendahl V, Schönhöfer P S

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1979 Mar;306(2):169-72. doi: 10.1007/BF00498987.

Abstract

Naloxone in high doses (60--240 mg/kg i.p.) produced a dose-dependent increase in cerebellar cGMP content of mice. The rise in cGMP content reached its maximum within 5 min and was of short duration. Short-lasting episodes of clonic seizures were noted after 240 mg/kg naloxone. Low doses of naloxone (5--10 mg/kg) had no effect on cerebellar cGMP content, but markedly potentiated the increase in cGMP induced by isoniazid. On the other hand, naloxone (5 mg/kg) partially antagonized the fall in cGMP elicited by diazepam, but had only a slight effect on the action of pentobarbital (30 mg/kg i.p.). These results support the assumption proposed by other authors that naloxone exerts GABA antagonistic effects aside from the potent opiate receptor antagonistic activity.

摘要

大剂量纳洛酮(腹腔注射60 - 240毫克/千克)可使小鼠小脑环磷酸鸟苷(cGMP)含量呈剂量依赖性增加。cGMP含量在5分钟内升至最高,且持续时间较短。注射240毫克/千克纳洛酮后出现了短暂的阵挛性癫痫发作。低剂量纳洛酮(5 - 10毫克/千克)对小脑cGMP含量无影响,但能显著增强异烟肼诱导的cGMP增加。另一方面,纳洛酮(5毫克/千克)部分拮抗了地西泮引起的cGMP下降,但对戊巴比妥(腹腔注射30毫克/千克)的作用仅有轻微影响。这些结果支持了其他作者提出的假设,即纳洛酮除了具有强大的阿片受体拮抗活性外,还具有γ-氨基丁酸(GABA)拮抗作用。

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