2. Academic Validation
  3. Neuroprotective and intraocular pressure lowering effects of dual-functional memantine nitrate MN-08 on the experimental models of glaucoma

Neuroprotective and intraocular pressure lowering effects of dual-functional memantine nitrate MN-08 on the experimental models of glaucoma

  • Sci Rep. 2025 Jul 3;15(1):23822. doi: 10.1038/s41598-025-06832-x.
Huihui Hu # 1 2 3 4,  Liangmiao Wu # 1 2 3 4,  Xiaodie Hu 2 3 4,  Minghua Wang 5,  Yewei Sun 2 3 4,  Gaoxiao Zhang 2 3 4,  Yuqiang Wang 2 3 4,  Peng Yi 6 7 8,  Zaijun Zhang 9 10 11
Affiliations

Affiliations

  • 1 Department of Intensive Care Unit, The First Affiliated Hospital of Jinan University and Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou, 511436, China.
  • 2 State Key Laboratory of Bioactive Molecules and Druggability Assessment, and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, and Institute of New Drug Research, Jinan University, Guangzhou, 511436, China.
  • 3 Guangdong-Hong Kong-Macau Joint Laboratory for Pharmacodynamic Constituents of TCM and New Drugs Research, and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University College of Pharmacy, Guangzhou, 511436, China.
  • 4 International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University College of Pharmacy, Guangzhou, 511436, China.
  • 5 Department of Neurology, Daqing People's Hospital, Daqing, 163319, China.
  • 6 State Key Laboratory of Bioactive Molecules and Druggability Assessment, and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, and Institute of New Drug Research, Jinan University, Guangzhou, 511436, China. yipeng2008@163.com.
  • 7 Guangdong-Hong Kong-Macau Joint Laboratory for Pharmacodynamic Constituents of TCM and New Drugs Research, and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University College of Pharmacy, Guangzhou, 511436, China. yipeng2008@163.com.
  • 8 International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University College of Pharmacy, Guangzhou, 511436, China. yipeng2008@163.com.
  • 9 State Key Laboratory of Bioactive Molecules and Druggability Assessment, and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-Cerebrovascular Diseases, and Institute of New Drug Research, Jinan University, Guangzhou, 511436, China. zaijunzhang@163.com.
  • 10 Guangdong-Hong Kong-Macau Joint Laboratory for Pharmacodynamic Constituents of TCM and New Drugs Research, and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University College of Pharmacy, Guangzhou, 511436, China. zaijunzhang@163.com.
  • 11 International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Jinan University College of Pharmacy, Guangzhou, 511436, China. zaijunzhang@163.com.
  • # Contributed equally.
PMID: 40610544 DOI: 10.1038/s41598-025-06832-x
Abstract

Glaucoma stands out as the primary cause of permanent blindness worldwide, marked by elevated intraocular pressure (IOP) and the deterioration of retinal ganglion cells (RGCs) within the optic nerve. This study aimed to investigate the therapeutic efficacy of MN-08, a novel memantine nitrate derivative, in experimental models of glaucoma. In the rat model of retinal ischemia-reperfusion injury, MN-08 prevented the reduction in retinal ganglion cell complex (GCC) thickness and RGC loss. Meanwhile, MN-08 reduced the protein levels of cleaved-caspase-3, Caspase-3, and Bax, while increasing the expression of Bcl-2 compared to the model group, indicating that MN-08 exerts an inhibitory effect on the Apoptosis of RGCs. Furthermore, MN-08 lowered IOP in the transient ocular hypertension and glaucoma rabbit models. MN-08 significantly increased cGMP levels in human trabecular meshwork cells (HTMCs). Elevation of cGMP induced by MN-08 was eliminated by ODQ. Moreover, MN-08 attenuated the protein levels of MLCK and p-MLC-2 in HTMCs induced by endothelin-1. Additionally, MN-08 exhibited favorable distribution profiles and pharmacokinetic parameters in normal rabbit ocular tissues following topical instillation. These findings indicate that MN-08 could antagonize NMDA receptors to protect RGCs and release NO to relax TM for the treatment of glaucoma.

Keywords

Glaucoma; Intraocular pressure; Memantine nitrate; Nitric oxide.

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