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局部应用天然麦角生物碱对正常眼压和α-糜蛋白酶诱导的高眼压兔眼压及房水动力学的比较研究

A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and alpha-chymotrypsin-induced ocular hypertensive rabbits.

作者信息

Puras Gustavo, Santafé Juan, Segarra José, Garrido Manuel, Melena José

机构信息

Department of Pharmacology, Universidad Autónoma de Tamaulipas, Tamaulipas, Mexico.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2007 Oct;245(10):1559-67. doi: 10.1007/s00417-007-0596-3. Epub 2007 May 16.

Abstract

BACKGROUND

Although it has been suggested that ergot derivatives may play a role in antiglaucoma therapy, little attention has been paid to the ocular hypotensive action of these drugs. Having previously reported that topical natural ergot alkaloids ergocristine alpha-ergocryptine and ergocornine dose-dependently reduce intraocular pressure in ocular normotensive and alpha-chymotrypsin-induced ocular hypertensive rabbits, the aim of the present work was to compare the effect of ergocristine, alpha-ergocryptine and ergocornine on the intraocular pressure and aqueous humor dynamics in ocular normotensive and alpha-chymotrypsin-induced ocular hypertensive rabbits, in order to further explore the ocular actions of these compounds.

METHODS

Experiments were conducted in albino ocular normotensive and hypertensive rabbits by intracameral injection of alpha-chymotrypsin. Intraocular pressure responses to drug vehicle and seven different doses of topical natural ergot alkaloids were examined, in order to obtain dose-response relationships for comparing the intraocular pressure-lowering effect and potency of these drugs. Tonographies were also performed to ascertain the actions of natural ergot alkaloids on aqueous humor dynamics.

RESULTS

All natural ergot alkaloids tested reduced intraocular pressure in a dose-related fashion. The ocular hypotensive effect was greater in alpha-chymotrypsin-induced ocular hypertensive rabbits for the three compounds tested. All natural ergot alkaloids tested decreased both tonographic outflow facility and, to a greater extent, aqueous humor inflow in ocular normotensive and in alpha-chymotrypsin-induced ocular hypertensive rabbits.

CONCLUSION

Taken together, our data suggest that these compounds decrease both tonographic outflow facility and, to a greater extent, aqueous humor inflow, which explains their final effect in ocular normotensive and in alpha-chymotrypsin-induced ocular hypertensive rabbits. Reductions in aqueous humor inflow observed after topical application of natural ergot alkaloids in alpha-chymotrypsin-induced ocular hypertensive rabbits can only be explained by a marked inhibition of active secretion of aqueous humor, since processes involved in aqueous humor formation may probably be altered after alpha-chymotrypsin injection.

摘要

背景

尽管有人提出麦角衍生物可能在抗青光眼治疗中发挥作用,但这些药物的降眼压作用却很少受到关注。此前曾报道,局部应用天然麦角生物碱麦角克碱、α-麦角隐亭和麦角柯宁能使眼压正常和α-糜蛋白酶诱导的高眼压兔眼压呈剂量依赖性降低。本研究的目的是比较麦角克碱、α-麦角隐亭和麦角柯宁对眼压正常和α-糜蛋白酶诱导的高眼压兔眼压及房水动力学的影响,以进一步探索这些化合物的眼部作用。

方法

通过前房内注射α-糜蛋白酶,在白化病眼压正常和高眼压兔身上进行实验。检测药物载体及七种不同剂量局部天然麦角生物碱的眼压反应,以获得剂量反应关系,比较这些药物的降眼压效果和效力。还进行了眼压描记法以确定天然麦角生物碱对房水动力学的作用。

结果

所有测试的天然麦角生物碱均以剂量相关方式降低眼压。对于所测试的三种化合物,在α-糜蛋白酶诱导的高眼压兔中,降眼压作用更强。所有测试的天然麦角生物碱均降低了眼压描记法测量的房水流出易度,并且在更大程度上降低了眼压正常和α-糜蛋白酶诱导的高眼压兔的房水流入。

结论

综合来看,我们的数据表明这些化合物降低了眼压描记法测量的房水流出易度,并且在更大程度上降低了房水流入,这解释了它们在眼压正常和α-糜蛋白酶诱导的高眼压兔中的最终作用。在α-糜蛋白酶诱导的高眼压兔中局部应用天然麦角生物碱后观察到的房水流入减少,只能通过房水活性分泌的显著抑制来解释,因为在注射α-糜蛋白酶后,房水生成过程可能已发生改变。

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