SUVN-502: A PURE 5-HT6 RECEPTOR ANTAGONIST ATTENUATES MEMORY DEFICITS INDUCED BY DIVERSE CHALLENGES

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that destroys the higher anatomical structures of the brain leading to dementia. The 5-HT6 receptor is an attractive target for the development of cognitive enhancers due to its unique localization and pharmacology. 5-HT6 receptor antagonists have been shown to modulate multiple neurotransmitter systems and thereby enhance cognition in preclinical studies. The effect of SUVN-502, a pure 5-HT6 receptor antagonist was evaluated in various rodent models of cognition. The procognitive effects of SUVN-502 were evaluated in object recognition task, the inter trial intervals being 24 or 48 h. SUVN-502 was administered during either acquisition or consolidation or retention phase of memory. The procognitive effects of SUVN-502 on scopolamine induced memory deficits were evaluated using the Morris water maze, radial arm maze and fear conditioning apparatus. SUVN-502 reversed both 24 and 48 h time induced memory deficits in the object recognition task. The memory enhancing effects were also observed when SUVN-502 was administered in any of the three phases of cognition. SUVN-502 reversed scopolamine induced memory deficits in the Morris water maze, radial maze and enhanced freezing time in the fear conditioning task. SUVN-502 reversed a combined scopolamine and MK-801 induced memory deficits in the object recognition task. SUVN-502 is a potent, selective, orally bioavailable and efficacious 5-HT6 receptor antagonist that holds promise in the treatment of dementia associated with hypocholinergic disease conditions such as Alzheimer's disease.