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α-甲基多巴可诱导大鼠产生对纳曲酮不敏感的抗伤害感受作用及运动迟缓。

Alpha-methyldopa induces a naltrexone-insensitive antinociception and hypomotility in rats.

作者信息

van Giersbergen P L, van Duinkerken E, Sweep C G, Wiegant V M, van Ree J M, de Jong W

机构信息

Rudolf Magnus Institute for Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.

出版信息

Br J Pharmacol. 1990 Mar;99(3):467-72. doi: 10.1111/j.1476-5381.1990.tb12951.x.

DOI:10.1111/j.1476-5381.1990.tb12951.x
PMID:2331579
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1917362/
Abstract
  1. This study served to investigate whether endogenous opioid peptides play a role in the putative antinociceptive and the sedative actions of alpha-methyldopa. 2. In conscious normotensive rats, alpha-methyldopa induced hypotension, starting around 1 h and reaching a maximum 3-4 h after administration. Pretreatment with naltrexone resulted in an inhibition of alpha-methyldopa-induced hypotension. 3. alpha-Methyldopa dose-dependently increased hot plate latency which became evident after a 4 h lag period and reaching a maximum effect at 6 h. The antinociceptive effect of alpha-methyldopa was not affected by naltrexone. 4. In a small open field, alpha-methyldopa dose-dependently suppressed locomotion and sniffing behaviour. These effects of alpha-methyldopa were apparent 1 h after administration and were naltrexone-insensitive. 5. No changes in the level of beta-endorphin-like immunoreactivity in plasma and cerebrospinal fluid were observed after administration of alpha-methyldopa. 6. The results indicate that endogenous opioid peptides are involved in the hypotensive action of alpha-methyldopa but not in alpha-methyldopa-induced hypomotility and antinociception.
摘要
  1. 本研究旨在探究内源性阿片肽是否在α-甲基多巴的假定镇痛和镇静作用中发挥作用。2. 在清醒的正常血压大鼠中，α-甲基多巴可诱发低血压，给药后约1小时开始出现，3 - 4小时达到最大值。用纳曲酮预处理可抑制α-甲基多巴诱发的低血压。3. α-甲基多巴剂量依赖性地增加热板潜伏期，4小时的延迟期后变得明显，6小时达到最大效应。α-甲基多巴的镇痛作用不受纳曲酮影响。4. 在一个小的旷场中，α-甲基多巴剂量依赖性地抑制运动和嗅探行为。α-甲基多巴的这些作用在给药后1小时明显，且对纳曲酮不敏感。5. 给予α-甲基多巴后，未观察到血浆和脑脊液中β-内啡肽样免疫反应性水平的变化。6. 结果表明，内源性阿片肽参与了α-甲基多巴的降压作用，但不参与α-甲基多巴诱导的运动减少和镇痛作用。
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e773/1917362/21e4e3ec69ab/brjpharm00258-0038-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e773/1917362/ef71c592dd20/brjpharm00258-0037-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e773/1917362/187f96e8f626/brjpharm00258-0037-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e773/1917362/bca0fc7983cd/brjpharm00258-0038-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e773/1917362/21e4e3ec69ab/brjpharm00258-0038-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e773/1917362/ef71c592dd20/brjpharm00258-0037-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e773/1917362/187f96e8f626/brjpharm00258-0037-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e773/1917362/bca0fc7983cd/brjpharm00258-0038-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e773/1917362/21e4e3ec69ab/brjpharm00258-0038-b.jpg

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Endorphin-related peptides in rat cerebrospinal fluid.
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beta-endorphin acting on the brainstem is involved in the antihypertensive action of clonidine and alpha-methyldopa in rats.
Circ Res. 1983 Aug;53(2):150-7. doi: 10.1161/01.res.53.2.150.
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Cardiovascular effects of beta-endorphin after microinjection into the nucleus tractus solitarii of the anaesthetised rat.将β-内啡肽微量注射到麻醉大鼠孤束核后对心血管系统的影响。
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Organization of endogenous opiate and nonopiate pain control systems.内源性阿片类和非阿片类疼痛控制系统的组织
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alpha-methyldopa reduces locomotor activity in rats via its metabolite, alpha-methylnorepinephrine, acting on alpha 2-adrenoceptors.α-甲基多巴通过其代谢产物α-甲基去甲肾上腺素作用于α2-肾上腺素能受体，从而降低大鼠的运动活性。
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