Back to Search
Start Over
SUVN-502, a novel, potent, pure, and orally active 5-HT6 receptor antagonist: pharmacological, behavioral, and neurochemical characterization.
- Source :
-
Behavioural pharmacology [Behav Pharmacol] 2019 Feb; Vol. 30 (1), pp. 16-35. - Publication Year :
- 2019
-
Abstract
- Research in Alzheimer's disease is going through a big turnaround. New palliative therapies are being reconsidered for the effective management of disease because of setbacks in the development of disease-modifying therapies. Serotonin 6 (5-HT6) receptor has long been pursued as a potential target for the symptomatic treatment of Alzheimer's disease. SUVN-502 is a novel 5-HT6 receptor antagonist (Ki=2.04 nmol/l) with high receptor affinity and high degree of selectivity. SUVN-502 at doses ranging from 1 to 10 mg/kg, per os (p.o.) demonstrated procognitive effects in various behavioral animal models (object recognition task, water maze, and radial arm maze), and it acts on three phases of cognition, viz., acquisition, consolidation, and retention (object recognition task). SUVN-502 (3 and 10 mg/kg, p.o.) modulated glutamate levels when administered alone (microdialysis). At doses ranging from 1 to 10 mg/kg p.o., SUVN-502 potentiated the effects of donepezil (microdialysis). SUVN-502 [1 mg/kg, intravenous (i.v.)] also potentiated pharmacological effects of memantine (1 mg/kg, i.v.) and/or donepezil (0.3 mg/kg, i.v.) (θ modulation). The beneficial effects of SUVN-502 on learning and memory might be mediated through the modulation of cholinergic and/or glutamatergic neurotransmission in relevant brain regions. In summary, behavioral, neurochemical, and electrophysiological outcomes indicate that SUVN-502 may augment the beneficial effects of donepezil and memantine combination.
- Subjects :
- Acetylcholine pharmacology
Animals
Brain Waves drug effects
CHO Cells
Cricetulus
Culture Media, Serum-Free pharmacology
Dizocilpine Maleate pharmacology
Donepezil pharmacology
Dose-Response Relationship, Drug
Electroencephalography
Glutamic Acid pharmacology
Male
Maze Learning drug effects
Memantine pharmacology
Memory Disorders chemically induced
Memory Disorders drug therapy
Microdialysis
Nootropic Agents pharmacology
Rats
Rats, Wistar
Receptors, Serotonin metabolism
Recognition, Psychology drug effects
Scopolamine toxicity
Serotonin metabolism
Behavior, Animal drug effects
Brain drug effects
Brain metabolism
Indoles pharmacology
Piperazines pharmacology
Serotonin Antagonists pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1473-5849
- Volume :
- 30
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Behavioural pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 29847336
- Full Text :
- https://doi.org/10.1097/FBP.0000000000000414