Giuffrida Stefania, Bucolo Claudio, Drago Filippo
Department of Experimental and Clinical Pharmacology, Ocular Pharmacology Centre, School of Medicine, University of Catania, Catania, Italy.
J Ocul Pharmacol Ther. 2003 Dec;19(6):527-34. doi: 10.1089/108076803322660440.
The role of nitric oxide (NO) in neuronal degeneration of glaucoma is well established, and drugs to inhibit NO production have been introduced in preclinical studies. The present experiments were made to investigate the pharmacological efficacy of a topical formulation of the nonselective nitric oxide synthase (NOS) inhibitor, nitro-L-arginine methyl ester (L-NAME), in an experimental model of glaucoma in rabbits. L-NAME was dissolved in an isotonic, mucoadhesive, viscosized, buffered solution in concentrations of 0.1%, 0.5%, or 1% (w/v). Ocular hypertension (of at least 15 mmHg compared to basal values) was induced by intra-ocular injection of alpha-chymotrypsin. The instillation of L-NAME topical formulations lowered the IOP of hypertensive rabbits in a dose-related manner, with a maximum drop of 12.0 mmHg 60 minutes after administration of the highest concentration. The area under the curve (AUC) of the DeltaIOP (mmHg) versus time (minutes) was 1050.3 +/- 141.7 and 15.1 +/- 2.5 for the 1% L-NAME-treated group and vehicle-treated group, respectively. No change was found in IOP or pupil diameter after instillation of L-NAME eye drops in normotensive rabbits. This study provides the first evidence that topical L-NAME significantly reduces the IOP in a model of ocular hypertension.
一氧化氮（NO）在青光眼神经元变性中的作用已得到充分证实，并且在临床前研究中已引入抑制NO生成的药物。本实验旨在研究非选择性一氧化氮合酶（NOS）抑制剂硝基-L-精氨酸甲酯（L-NAME）局部制剂在兔青光眼实验模型中的药理疗效。L-NAME以0.1%、0.5%或1%（w/v）的浓度溶解于等渗、粘膜粘附、增粘、缓冲溶液中。通过眼内注射α-糜蛋白酶诱导眼压升高（与基础值相比至少升高15 mmHg）。局部滴注L-NAME制剂可使高血压兔的眼压以剂量相关的方式降低，在给予最高浓度后60分钟，眼压最大降幅为12.0 mmHg。1% L-NAME治疗组和赋形剂治疗组的DeltaIOP（mmHg）与时间（分钟）曲线下面积（AUC）分别为1050.3±141.7和15.1±2.5。在正常血压兔中滴注L-NAME滴眼液后，眼压或瞳孔直径未发现变化。本研究提供了首个证据，表明局部应用L-NAME可在高眼压模型中显著降低眼压。
