JM-20 protects memory acquisition and consolidation on scopolamine model of cognitive impairment

Neurol Res. 2019 May;41(5):385-398. doi: 10.1080/01616412.2019.1573285. Epub 2019 Mar 1.


Objective: JM-20, a novel hybrid synthetic molecule, has been reported to have antioxidant, mitoprotective, anti-excitotoxic, anti-apoptotic and anti-inflammatory properties. However, the neuroprotective effect of JM-20 against memory impairment in preclinical AD-like models has not been analyzed. The aim of this study was to evaluate the potential neuroprotection of JM-20 that preserves essential memory process from cholinergic dysfunction and other molecular damages.

Methods: The effects of JM-20 on scopolamine (1 mg/kg)-induced cognitive disorders were studied. Male Wistar rats (220-230 g) were treated with JM-20 and/or scopolamine, and behavioral tasks were performed. The AChE activity, superoxide dismutase activity, catalase activity, MDA and T-SH level on brain tissue were determined by spectrophotometric methods. Mitochondrial functionality parameters were measured after behavioral tests. Histological analyses on hippocampus and prefrontal cortex were processed with hematoxylin and eosin, and neuronal and axonal damage were determined.

Results: The behavioral, biochemical and histopathological studies revealed that oral pre-treatment with JM-20 (8 mg/kg) significantly attenuated the scopolamine-induced memory deficits, mitochondrial malfunction, oxidative stress, and prevented AChE hyperactivity probably due to specific inhibition of AChE enzyme. It was also observed marked histological protection on hippocampal and prefrontal-cortex regions.

Conclusions: The multimodal action of this molecule could mediate the memory protection here observed and suggest that it may modulate different pathological aspects of memory deficits associated with AD in humans.

Keywords: JM-20; cognitive impairments; neurodegeneration; neuroprotection; scopolamine.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Antioxidants / metabolism
  • Benzodiazepines / pharmacology*
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cholinesterase Inhibitors / pharmacology*
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Lipid Peroxidation / drug effects
  • Lipid Peroxidation / physiology
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Memory Disorders / drug therapy
  • Memory Disorders / metabolism
  • Memory Disorders / pathology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Niacin / analogs & derivatives*
  • Niacin / pharmacology
  • Nootropic Agents / pharmacology*
  • Random Allocation
  • Rats, Wistar
  • Scopolamine


  • 3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro-1H-pyrido(2,3-b)(1,5)benzodiazepine
  • Antioxidants
  • Cholinesterase Inhibitors
  • Nootropic Agents
  • Benzodiazepines
  • Niacin
  • Scopolamine
  • Acetylcholinesterase