Potential neurotoxicity of a novel aminoacridine analogue
| Autor: | TM Walker, C.K. Atterwill, BB Dewhurst, B. Starr |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Neutral red Aminoacridine Aché Health Toxicology and Mutagenesis Neurotoxins Scopolamine Toxicology Mice Neuroblastoma Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Memory In vivo Internal medicine Tumor Cells Cultured medicine Animals Analysis of Variance Behavior Animal Aminoacridines Chemistry Neurotoxicity General Medicine medicine.disease Acetylcholinesterase In vitro language.human_language 030104 developmental biology Endocrinology Neutral Red Tacrine Exploratory Behavior language Metallothionein Cholinesterase Inhibitors Oxidation-Reduction 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Human & Experimental Toxicology. 14:469-474 |
| ISSN: | 1477-0903 0960-3271 |
| DOI: | 10.1177/096032719501400601 |
| Popis: | 1 A class of compounds, 9-aminoacridines, have long been known to be reversible inhibitors of acetyl cholinesterase (AChE - EC 3.1.1.7), the most familiar of which is 9-amino-1,2,3,4-tetrahydroacridine (Tacrine). 2 A novel aminoacridine was synthesised: - 2-tertiary butyl-9-amino-1,2,3,4-tetrahydroacridine (2tBuTHA). 3 In vitro comparisons of the acetylcholinesterase inhibitory potential and neurotoxicity compared to Tacrine were performed using a chemically differentiated neuroblastoma cell line (Neuro 2A). 2tBuTHA, but not Tacrine, was cytotoxic to the neural cell following 20 h exposure, despite being the least potent AChE inhibitor (IC80 AChE 12.53 μM +/- 1.14 s.e.m., Neutral Red Uptake IC50 9.53 μM +/- 0.98 s.e.m., MTT Reduction IC80 14.6 μM +/- 1.43 s.e.m.). 4 In vivo studies used a novel application of a five arm radial maze to assess neuropharmacological effects on working memory in control and Scopolamine (1 mg kg-1 i.p.) treated mice. There was an impairment of short term cognitive function with 2tBuTHA (15 mg kg -1 i.p.), but not Tacrine (10 mg kg-1 i.p.) which improved the Scopolamine deficit as expected. 5 This combined in vitro and in vivo data infers a neuro toxic property for the novel compound 2tBuTHA, a close structural analogue of Tacrine. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|