硝苯地平增强环氧化酶抑制剂对牛睫状肌的松弛作用。

Nifedipine enhances the relaxant effects of cyclo-oxygenase inhibitors on the bovine ciliary muscle.

作者信息

Toker Mustafa, Bagcivan Ihsan, Topalkara Aysen, Karadas Baris, Durmus Nedim, Parlak Ahmet, Kaya Tijen

机构信息

Department of Ophthalmology, Cumhuriyet University School of Medicine, Sivas, Turkey.

出版信息

J Ocul Pharmacol Ther. 2008 Dec;24(6):537-41. doi: 10.1089/jop.2007.0129.

DOI:10.1089/jop.2007.0129

PMID:19046136

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2958440/

Abstract

BACKGROUND/AIMS: The inhibition of cyclo-oxygenase (COX) enzymes and the blockade of Ca (2+) channels play an important role in the regulation of smooth muscle relaxation. This study was designed to investigate the relaxant effects of celecoxib, DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl)phenyl-2(5H)-furanone), and indomethacin, cyclo-oxygenase (COX-1 and -2) inhibitors, in the absence or presence of a nifedipine, L-type Ca(2+) channel blocker, on bovine ciliary muscle.

METHODS

Ciliary muscle strips (n = 12) were mounted in organ baths and tested for changes in isometric tension in response to celecoxib, DFU, and indomethacin. The relaxant effects of celecoxib, DFU, and indomethacin on carbachol-induced contractions in the presence or absence of nifedipine were investigated.

RESULTS

Celecoxib (10(-7)-10(-4) M), DFU (10(-7)-10(-4) M), indomethacin (10(-7)-10(-4) M), and nifedipine (10(-7)-10(-4) M) inhibited the carbachol-induced contractions in a concentration-dependent manner. The E(max) value of indomethacin was significantly higher than the E(max) values of celecoxib and DFU in ciliary muscle (P < 0.05), with no significant change in pD(2) values (P > 0.05). The relaxation responses by celecoxib, DFU, and indomethacin were significantly increased in the presence of nifedipine (10(-6) M). There were no significant differences between pEC50 and values of celecoxib, DFU, and indomethacin in the absence of nifedipine (10(-6) M) (P > 0.05), but E(max)values were significantly increased (P < 0.05).

CONCLUSIONS

These results suggest that the celecoxib, DFU, and indomethacin cause relaxation in ciliary muscle precontracted with carbachol. Blockade of calcium channels with nifedipine in ciliary muscle may increase the relaxant effect of celecoxib, DFU, and indomethacin. The topical or systemic use of celecoxib, DFU, and indomethacin with nifedipine can cause blurred near vision due to ciliary muscle relaxation, and in ocular pain conditions caused by ciliary spasm, the pain can be decreased more easily by combined use of these drugs.

摘要

背景/目的：环氧化酶（COX）酶的抑制作用以及钙（Ca2+）通道的阻断在平滑肌舒张调节中发挥着重要作用。本研究旨在探讨塞来昔布、DFU（5,5 - 二甲基 - 3 -（3 - 氟苯基）- 4 -（4 - 甲磺酰基）苯基 - 2（5H）- 呋喃酮）和吲哚美辛（环氧化酶（COX - 1和 - 2）抑制剂）在不存在或存在硝苯地平（一种L型钙通道阻滞剂）的情况下对牛睫状肌的舒张作用。

方法

将睫状肌条（n = 12）安装在器官浴槽中，检测其对塞来昔布、DFU和吲哚美辛的等长张力变化。研究了在存在或不存在硝苯地平的情况下，塞来昔布、DFU和吲哚美辛对卡巴胆碱诱导的收缩的舒张作用。

结果

塞来昔布（10^(-7) - 10^(-4) M）、DFU（10^(-7) - 10^(-4) M）、吲哚美辛（10^(-7) - 10^(-4) M）和硝苯地平（10^(-7) - 10^(-4) M）以浓度依赖性方式抑制卡巴胆碱诱导的收缩。在睫状肌中，吲哚美辛的E(max)值显著高于塞来昔布和DFU的E(max)值（P < 0.05），而pD(2)值无显著变化（P > 0.05）。在存在硝苯地平（10^(-6) M）的情况下，塞来昔布、DFU和吲哚美辛的舒张反应显著增强。在不存在硝苯地平（10^(-6) M）时，塞来昔布、DFU和吲哚美辛的pEC50值之间无显著差异（P > 0.05），但E(max)值显著增加（P < 0.05）。

结论

这些结果表明，塞来昔布、DFU和吲哚美辛可使预先由卡巴胆碱收缩的睫状肌舒张。在睫状肌中用硝苯地平阻断钙通道可能会增强塞来昔布、DFU和吲哚美辛的舒张作用。局部或全身使用塞来昔布、DFU和吲哚美辛联合硝苯地平可能会因睫状肌舒张而导致近视力模糊，并且在由睫状肌痉挛引起的眼部疼痛情况下，联合使用这些药物可更轻易地减轻疼痛。