Department of Pharmacology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Invest Ophthalmol Vis Sci. 2021 Jun 1;62(7):8. doi: 10.1167/iovs.62.7.8.
Patients that medicate with antidepressants commonly report dryness of eyes. The cause is often attributed to the anticholinergic properties of the drugs. However, regulation of tear production includes a substantial reflex-evoked component and is regulated via distinct centers in the brain. Further, the anticholinergic component varies greatly among antidepressants with different mechanisms of action. In the current study it was wondered if acute administration of antidepressants can disturb production of tears by affecting the afferent and/or central pathway.
Tear production was examined in vivo in anesthetized rats in the presence or absence of the tricyclic antidepressant (TCA) clomipramine or the selective serotonin reuptake inhibitor (SSRI) escitalopram. The reflex-evoked production of tears was measured by challenging the surface of the eye with menthol (0.1 mM) and cholinergic regulation was examined by intravenous injection with the nonselective muscarinic agonist methacholine (1-5 µg/kg).
Acute administration of clomipramine significantly attenuated both reflex-evoked and methacholine-induced tear production. However, escitalopram only attenuated reflex-evoked tear production, while methacholine-induced production of tears remained unaffected.
This study shows that antidepressants with different mechanisms of action can impair tear production by attenuating reflex-evoked signaling. Further, antimuscarinic actions are verified as a likely cause of lacrimal gland hyposecretion in regard to clomipramine but not escitalopram. Future studies on antidepressants with different selectivity profiles and mechanisms of action are required to further elucidate the mechanisms by which antidepressants affect tear production.
使用抗抑郁药治疗的患者常报告眼睛干涩。其原因通常归因于药物的抗胆碱能特性。然而，泪液的产生受调节包括一个实质性的反射诱发成分，并通过大脑中的不同中心进行调节。此外，不同作用机制的抗抑郁药的抗胆碱能成分差异很大。在目前的研究中，人们想知道抗抑郁药的急性给药是否会通过影响传入和/或中枢途径来干扰泪液的产生。
在麻醉大鼠中体内检查在存在或不存在三环抗抑郁药（TCA）氯米帕明或选择性 5-羟色胺再摄取抑制剂（SSRI）依地普仑的情况下泪液的产生。通过用薄荷醇（0.1mM）刺激眼睛表面来测量反射诱发的泪液产生，并且通过静脉内注射非选择性毒蕈碱激动剂氯化甲酰胆碱（1-5μg/kg）来检查胆碱能调节。
氯米帕明的急性给药显著减弱了反射诱发和氯化甲酰胆碱诱导的泪液产生。然而，依地普仑仅减弱了反射诱发的泪液产生，而氯化甲酰胆碱诱导的泪液产生不受影响。
本研究表明，作用机制不同的抗抑郁药可以通过减弱反射诱发的信号来损害泪液产生。此外，抗毒蕈碱作用被证实为氯米帕明而不是依地普仑导致泪腺分泌不足的可能原因。需要进一步研究具有不同选择性特征和作用机制的抗抑郁药，以进一步阐明抗抑郁药影响泪液产生的机制。
