Safety and effect of topical neostigmine ophthalmic solution in animal models

Abstract The study aimed to evaluate the safety and effect of various dosages of topical neostigmine ophthalmic solution (TNOS) in animal models and establish a recommended dosage for further studies on myasthenia gravis (MG) diagnosis. A placebo-controlled, sequential ascending dose study was condu...

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Main Authors: Chuthamas Ongprakobkul, Supharat Jariyakosol, Supanut Apinyawasisuk, Kasem Rattanapinyopituk, Pajaree Chariyavilaskul, Kornvalee Meesilpavikkai, Yuda Chongpison
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-16328-3
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author Chuthamas Ongprakobkul
Supharat Jariyakosol
Supanut Apinyawasisuk
Kasem Rattanapinyopituk
Pajaree Chariyavilaskul
Kornvalee Meesilpavikkai
Yuda Chongpison
author_facet Chuthamas Ongprakobkul
Supharat Jariyakosol
Supanut Apinyawasisuk
Kasem Rattanapinyopituk
Pajaree Chariyavilaskul
Kornvalee Meesilpavikkai
Yuda Chongpison
author_sort Chuthamas Ongprakobkul
collection DOAJ
description Abstract The study aimed to evaluate the safety and effect of various dosages of topical neostigmine ophthalmic solution (TNOS) in animal models and establish a recommended dosage for further studies on myasthenia gravis (MG) diagnosis. A placebo-controlled, sequential ascending dose study was conducted in healthy rabbits. Eighteen eyes were randomized to receive one of three concentrations (1.0, 1.5, and 2.5 mg/mL) of TNOS. Pupillary sizes over time were compared with control group that received normal saline solution (NSS). Mean pupillary size of the 1.5 mg/mL group was significantly smaller than control at 30 to 180 min after instillation (maximal mean difference (TNOS - NSS); mMD − 2.58, 95% confidence interval (95% CI) -4.24 to -0.93, p = 0.006). The mean pupillary size of the 2.5 mg/mL group was significantly smaller than the control at 60 to 90 min (mMD − 3.13, 95% CI -5.07 to -1.18, p = 0.005). No significant difference in pupillary size between 1.5 and 2.5 mg/mL groups was observed at any time points. No systemic or ocular complications were observed in any concentration. The 1.5 mg/mL TNOS was the lowest efficacious dose in this study without adverse effects and was considered a promising starting dose for further MG studies.
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spelling doaj-art-b0209a1f3d0d4007b4e2ef1cde4a0caf2025-08-24T11:25:45ZengNature PortfolioScientific Reports2045-23222025-08-0115111110.1038/s41598-025-16328-3Safety and effect of topical neostigmine ophthalmic solution in animal modelsChuthamas Ongprakobkul0Supharat Jariyakosol1Supanut Apinyawasisuk2Kasem Rattanapinyopituk3Pajaree Chariyavilaskul4Kornvalee Meesilpavikkai5Yuda Chongpison6Department of Ophthalmology, Faculty of Medicine, Chulalongkorn UniversityDepartment of Ophthalmology, Faculty of Medicine, Chulalongkorn UniversityDepartment of Ophthalmology, Faculty of Medicine, Chulalongkorn UniversityDepartment of Pathology, Faculty of Veterinary Science, Chulalongkorn UniversityCenter of Excellence in Clinical Pharmacokinetics and Pharmacogenomics, Department of Pharmacology, Faculty of Medicine, Chulalongkorn UniversityDepartment of Microbiology, Faculty of Medicine, Chulalongkorn UniversityBiostatistics Excellence Center, Research Affairs and Center of Excellence for Skin and Allergy Research, Faculty of Medicine, Chulalongkorn UniversityAbstract The study aimed to evaluate the safety and effect of various dosages of topical neostigmine ophthalmic solution (TNOS) in animal models and establish a recommended dosage for further studies on myasthenia gravis (MG) diagnosis. A placebo-controlled, sequential ascending dose study was conducted in healthy rabbits. Eighteen eyes were randomized to receive one of three concentrations (1.0, 1.5, and 2.5 mg/mL) of TNOS. Pupillary sizes over time were compared with control group that received normal saline solution (NSS). Mean pupillary size of the 1.5 mg/mL group was significantly smaller than control at 30 to 180 min after instillation (maximal mean difference (TNOS - NSS); mMD − 2.58, 95% confidence interval (95% CI) -4.24 to -0.93, p = 0.006). The mean pupillary size of the 2.5 mg/mL group was significantly smaller than the control at 60 to 90 min (mMD − 3.13, 95% CI -5.07 to -1.18, p = 0.005). No significant difference in pupillary size between 1.5 and 2.5 mg/mL groups was observed at any time points. No systemic or ocular complications were observed in any concentration. The 1.5 mg/mL TNOS was the lowest efficacious dose in this study without adverse effects and was considered a promising starting dose for further MG studies.https://doi.org/10.1038/s41598-025-16328-3NeostigmineMyasthenia gravisEyedropPupilAnimal models
spellingShingle Chuthamas Ongprakobkul
Supharat Jariyakosol
Supanut Apinyawasisuk
Kasem Rattanapinyopituk
Pajaree Chariyavilaskul
Kornvalee Meesilpavikkai
Yuda Chongpison
Safety and effect of topical neostigmine ophthalmic solution in animal models
Scientific Reports
Neostigmine
Myasthenia gravis
Eyedrop
Pupil
Animal models
title Safety and effect of topical neostigmine ophthalmic solution in animal models
title_full Safety and effect of topical neostigmine ophthalmic solution in animal models
title_fullStr Safety and effect of topical neostigmine ophthalmic solution in animal models
title_full_unstemmed Safety and effect of topical neostigmine ophthalmic solution in animal models
title_short Safety and effect of topical neostigmine ophthalmic solution in animal models
title_sort safety and effect of topical neostigmine ophthalmic solution in animal models
topic Neostigmine
Myasthenia gravis
Eyedrop
Pupil
Animal models
url https://doi.org/10.1038/s41598-025-16328-3
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