Department of Pharmaceutical Sciences, Midwestern University Chicago College of Pharmacy, Downers Grove, Ill. 60515, USA.
Pharmacology. 2011;88(5-6):233-41. doi: 10.1159/000331880. Epub 2011 Oct 12.
Centhaquin is a centrally acting hypotensive drug like clonidine. Clonidine also produces analgesia and hypothermia in mice and potentiates morphine analgesia. Clonidine analgesia is blocked by idazoxan and naloxone while it is potentiated by BQ123 and sulfisoxazole. This study was conducted to determine the analgesic and hypothermic properties of centhaquin, and to assess whether it potentiates morphine analgesia. Yohimbine (α(2)-adrenergic antagonist), idazoxan (imidazoline/α(2)-adrenergic antagonist), naloxone (opioid antagonist), and BQ123 and sulfisoxazole (endothelin ET(A) antagonists) were used to study the involvement of these receptors in centhaquin analgesia and hypothermia.
Analgesic (tail flick and hot-plate tests) latencies and body temperatures were measured in male Swiss Webster mice treated with vehicle plus centhaquin, antagonists plus centhaquin or centhaquin plus morphine.
Centhaquin produced dose-dependent analgesia which was partially blocked by yohimbine, idazoxan and naloxone. BQ123 and sulfisoxazole did not affect centhaquin analgesia. Morphine analgesia was not potentiated by centhaquin. Centhaquin produced mild hypothermia which was not blocked by yohimbine, idazoxan, naloxone, BQ123 or sulfisoxazole.
This is the first report demonstrating the analgesic activity of centhaquin. The α(2)-adrenergic, imidazoline and opioid receptors are involved in mediating centhaquin analgesia. Endothelin ET(A) receptors do not play a role in centhaquin analgesia; centhaquin does not augment morphine analgesia.
Centhaquin 是一种作用于中枢的降压药物，类似于可乐定。可乐定也能在小鼠中产生镇痛和降温作用，并增强吗啡的镇痛作用。可乐定的镇痛作用被伊达唑和纳洛酮阻断，而被 BQ123 和磺胺异恶唑增强。本研究旨在确定 Centhaquin 的镇痛和降温特性，并评估其是否增强吗啡的镇痛作用。育亨宾（α2-肾上腺素能拮抗剂）、伊达唑（咪唑啉/α2-肾上腺素能拮抗剂）、纳洛酮（阿片受体拮抗剂）以及 BQ123 和磺胺异恶唑（内皮素 ET(A)拮抗剂）被用于研究这些受体在 Centhaquin 镇痛和降温中的作用。
在雄性瑞士 Webster 小鼠中，用 vehicle 加 Centhaquin、拮抗剂加 Centhaquin 或 Centhaquin 加吗啡处理后，测量镇痛（尾巴摆动和热板试验）潜伏期和体温。
Centhaquin 产生剂量依赖性的镇痛作用，部分被育亨宾、伊达唑和纳洛酮阻断。BQ123 和磺胺异恶唑不影响 Centhaquin 的镇痛作用。吗啡的镇痛作用没有被 Centhaquin 增强。Centhaquin 产生轻微的降温作用，育亨宾、伊达唑、纳洛酮、BQ123 或磺胺异恶唑均不能阻断。
这是首次报道 Centhaquin 的镇痛活性。α2-肾上腺素能、咪唑啉和阿片受体参与介导 Centhaquin 的镇痛作用。内皮素 ET(A)受体在 Centhaquin 的镇痛作用中不起作用；Centhaquin 不会增强吗啡的镇痛作用。
