Variable effects of previously untested muscarinic receptor antagonists on experimental myopia
Variable effects of previously untested muscarinic receptor antagonists on experimental myopia
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DOI：
10.1167/iovs.02-0796
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发表时间：
2003-03-01
影响因子：
4.4
通讯作者：
Stell, WK
中科院分区：
文献类型：
--
作者：
Luft, WA;Ming, Y;Stell, WK
目的.玻璃体内注射阿托品、哌仑西平和欣巴辛可预防形觉剥夺性近视（FDM）。这些药物抗近视的机制和作用部位尚不清楚。为了进一步阐明这种机制是否是毒蕈碱的，对其他几种毒蕈碱拮抗剂进行了测试。不同浓度的阿托品、哌仑西平、右替米特、东莨菪碱、托品酰胺、苯托品、双环胺、没食子胺、甲哌唑酯、羟苯铵、丙胺太林、丙环利定、4-二苯基乙酰氧基-N-甲基哌啶（4-DAMP）、六氢-硅杂-地芬尼多（HHSiD）、对氟六氢-硅杂-地芬尼多将pf-HHSiD、甲氧胺、AFDX-116和二苯羟乙酸奎宁环酯（QNB）以48小时的间隔注射到来亨鸡的带护目镜的眼睛中三次。另一只对照眼接受盐水。对照动物的双眼接受盐水。最后一次注射后24小时，测量屈光度、眼重和眼轴长度，并准备眼进行显微镜检查。除阿托品和哌仑西平外，只有氧苯溴铵可完全挽救FDM（戴护目镜与对照组;平均值+/- SD;屈光差异：-9.50 +/- 0.22 D vs. 0.83 +/- 0.31 D，P < 0.001;湿重差异：75.67 +/- 3.84 mg vs. 2.33 +/- 6.14 mg，P < 0.001;轴向长度差异：0.80 +/- 0.05 mm vs. 0.03 +/- 0.04 mm，P < 0.001）。羟苯铵治疗的视网膜没有显示出损伤。在其他化合物中，有几种引起部分拯救和/或损伤视网膜，而其他化合物则没有效果。羟苯铵可预防雏鸡FDM。其他化合物的无效或部分有效性，加上预防FDM所需的高浓度有效化合物，表明毒蕈碱拮抗剂可以在远离视网膜的部位或通过非毒蕈碱机制预防FDM，其中只有一些药物发挥作用。
PURPOSE. Atropine, pirenzepine, and himbacine prevent form-deprivation myopia (FDM) when administered intravitreously. The mechanisms and sites of action of these drugs against myopia are not clear. To shed further light on whether this mechanism is muscarinic, several other muscarinic antagonists were tested.METHODS. Various concentrations of atropine, pirenzepine, dexetimide, scopolamine, tropicamide, benztropine, dicyclomine, gallamine, mepenzolate, oxyphenonium, propantheline, procyclidine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), hexahydro-sila-difenidol (HHSiD),p-fluorohexahydro-sila-difenidol (pf-HHSiD), methoctramine, AFDX-116, and quinuclidinyl benzilate (QNB) were injected into goggled eyes of Leghorn cockerels three times at 48-hour intervals. Fellow control eyes received saline. Control animals received saline in both eyes. Twenty-four hours after final injections, refraction, eye weight, and axial length were measured, and eyes were prepared for microscopy.RESULTS. Other than atropine and pirenzepine, only oxyphenonium caused full rescue from FDM (goggled versus control; mean +/- SD; refraction differences: -9.50 +/- 0.22 D vs. 0.83 +/- 0.31 D, P < 0.001; wet weight differences: 75.67 +/- 3.84 mg vs. 2.33 +/- 6.14 mg, P < 0.001; axial length differences: 0.80 +/- 0.05 mm vs. 0.03 +/- 0.04 mm, P < 0.001). Oxyphenonium-treated retinas showed no damage. Of the other compounds, several elicited partial rescue and/or damaged the retina, whereas others had no effect.CONCLUSIONS. Oxyphenonium prevents FDM in chicks. The ineffectiveness or partial effectiveness of other compounds, coupled with the high concentrations of effective compounds required to prevent FDM, suggests that muscarinic antagonists act to prevent FDM, either at sites distant from the retina, or through a nonmuscarinic mechanism, on which only some of these drugs act.