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Occulohypotensive Effect Of Torasamide In Experimental Glaucoma

机译:妥拉沙胺在实验性青光眼中的眼球降压作用

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Glaucoma is a disease of eye that is characterized by an increase in intraocular pressure (IOP). We have studied the effect of torasamide (1%) on intraocular pressure (IOP) in experimentally induced acute and chronic models of glaucoma in rabbits. Some of the possibilities regarding mechanism of action involved were also studied.Acute glaucoma was induced by intravenous administration of 5% dextrose. Pretreatment with topical torasemide (1%) prevented acute rise in IOP induced by intravenous administration of 5% dextrose infusion. Chronic glaucoma model was produced by injection of freshly prepared 50 unit of α-chymotrypsin in 0.1 ml of sterile saline in the posterior chamber of the eye. Torasemide (1%) (From 33.06±0.73 to 19.96±0.1 mmHg) and pilocarpine (1%) (From 30.13±0.40 to 20.8±0.04 mmHg) produced a significant fall in intraocular pressure in rabbits with α-chymotrypsin induced ocular hypertension. Pretreatment with indomethacin (1%) (A prostaglandin synthesis inhibitor) blocked the IOP lowering effect of torasemide (1%). Pretreatment with pilocarpine (1%) did not produce any significant change in IOP lowering action of torasemide (1%). Our data suggest that torasemide showed oculohypotensive effect probably by enhancing aqueous humor outflow. Introduction Glaucoma is a multifactorial disease with a number of elements contributing to its development. An elevation of intraocular pressure (IOP) is a prominent component in optic nerve damage, which is the hallmark of glaucoma. If the elevated IOP is inadequately treated, progressive blindness may result.Various drugs used in treatment of glaucoma 1 are parasympathomimetics,β-adrenoceptor blockers, carbonic anhydrase inhibitors, α2-adrenoceptor agonists, prostaglandin analogues and angiotensin converting enzyme inhibitors 2 (ACE inhibitors). Timolol eye drops are a golden standard in the treatment of glaucoma. However, timolol is known to get into systemic circulation and causes various systemic effects. 3 Although glaucoma is known to be a serious chronic eye disease, an ideal agent to be used in this disease is still not available and there has been a constant urge for the discovery of newer drugs.Tingey et al. (1992) observed that topical application of a loop diuretic, ethacrynic acid in the eyes of rabbits and monkeys, reduced intraocular pressure. 4 Neumann et al. (1992) reported that a single intracameral injection of ethacrynic acid reduced IOP in patients with glaucoma. 5 In the present study, we investigated the effect of torasemide on IOP in rabbits and possible mechanism of action of this agent. Materials And Methods Experimental animals New Zealand white rabbits of either sex weighing 1.5 to 2.5 kg, (Zydus Research Center, Ahmedabad, India) housed under well controlled conditions of temperature (22±2°C), humidity (55±5%) and 12/12-h light dark cycle were given access to food and water ad libitum. The protocol of the experiment was approved by the Institutional Animal Ethical Committee as per the guidance of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Ministry of Social Justice and Empowerment, Government of India. Acute glaucoma modelRabbits weighing 1.5 to 2.5 kg were used for the study. The basal intraocular pressure was measured by tonometer (Schiotz type indentation tonometer) and the drug solutions prepared in suitable solvents were instilled topically into the left eye. The drug solutions used in the study were torasemide (1% in PEG 400) and pilocarpine (1%, FDC Ltd., India). The right eye received the vehicle, which served as control. After 15 minutes of drug administration, 5% dextrose solution (15 ml/kg) was intravenously infused through marginal ear vein. The Intra ocular pressure (IOP) changes were recorded every 15 minutes till the pressure became normal.Chronic glaucoma model Rabbits weighing of 1.5 to 2.5 kg (either sex) were sedated with diazepam (1 mg/kg i.v.) and anaesthetized with ketamine (25 mg
机译:青光眼是一种眼内疾病,其特征在于眼内压(IOP)升高。我们已经在实验性诱发的青光眼家兔的急性和慢性模型中研究了torasamide(1%)对眼压(IOP)的影响。还研究了涉及作用机制的一些可能性。静脉注射5%葡萄糖可诱发急性青光眼。局部用妥拉塞米(1%)预处理可预防静脉注射5%葡萄糖输注引起的眼压急剧上升。慢性青光眼模型是通过将新鲜制备的50单位α-胰凝乳蛋白酶注射到眼后房的0.1 ml无菌盐水中制成的。在α-胰凝乳蛋白酶诱导的高眼压兔中,托拉塞米(1%)(从33.06±0.73至19.96±0.1 mmHg)和毛果芸香碱(1%)(从30.13±0.40至20.8±0.04 mmHg)导致眼内压显着下降。用吲哚美辛(1%)(一种前列腺素合成抑制剂)进行预处理可阻断托拉塞米(1%)的降低眼压。毛果芸香碱(1%)的预处理对妥拉塞米(1%)的眼压降低作用没有产生任何显着变化。我们的数据表明,妥拉塞米可能通过增强房水流出而显示出降血压作用。引言青光眼是一种多因素疾病,其发展涉及许多因素。眼内压(IOP)升高是视神经损害的重要组成部分,这是青光眼的标志。如果IOP升高未得到充分治疗,可能会导致进行性失明。治疗青光眼1的各种药物包括拟副交感神经药,β-肾上腺素受体阻滞剂,碳酸酐酶抑制剂,α2-肾上腺素受体激动剂,前列腺素类似物和血管紧张素转化酶抑制剂2 。替莫洛尔滴眼液是治疗青光眼的黄金标准。然而,已知噻吗洛尔会进入全身循环并引起多种全身作用。 3尽管已知青光眼是一种严重的慢性眼病,但仍无法获得用于该疾病的理想药物,并且不断有发现新药的迫切需求。Tingey等人。 (1992年)观察到在兔子和猴子的眼睛局部应用a利尿剂,乙炔酸可以降低眼压。 4 Neumann等。 (1992)报道单次前房注射乙炔酸可降低青光眼患者的眼压。 5在本研究中,我们研究了托拉塞米对家兔眼压的影响及其可能的作用机理。材料和方法实验动物体重在1.5到2.5千克之间的新西兰白兔(印度艾哈迈达巴德Zydus研究中心),在温度(22±2°C),湿度(55±5%)和12 / 12-h的黑暗-黑暗周期可随意获得食物和水。实验方案已根据印度政府社会正义与授权部动物控制与监督委员会(CPCSEA)的指导,由机构动物伦理委员会批准。急性青光眼模型研究使用重1.5至2.5公斤的兔子。用眼压计(Schiotz型压痕眼压计)测量基础眼内压,并将在合适溶剂中制备的药物溶液局部滴入左眼。研究中使用的药物溶液为妥拉塞米(PEG 400中为1%)和毛果芸香碱(印度FDC Ltd.中为1%)。右眼接收到车辆,作为控制。给药15分钟后,通过耳缘静脉静脉注射5%葡萄糖溶液(15 ml / kg)。每15分钟记录一次眼内压(IOP)的变化,直到压力恢复正常为止。慢性青光眼模型体重1.5至2.5 kg(两性)的兔子用地西epa(1 mg / kg iv)镇静,并用氯胺酮(25)麻醉毫克

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