Authors: Jayaprakash Tadiparthi, Narender Ganuga, Venkata Ramalingayya Grandhi, Rajesh Babu Medapati, Venkatesh Kamuju, Sudhakar Gandipudi, Veena Reballi, Pradeep Jayarajan, Ramakrishna Nirogi
Published: 2020-12-07
DOI: 10.1002/alz.039312
Source: Full article
AbstractBackgroundBehavioral and psychological symptoms of dementia (BPSD) are the common behavioral changes observed in patients with Alzheimer’s disease (AD). More than 90% of people with dementia develop at least one BPSD over a 5 years time period with around 85% of patients experiences serious clinical implications. Serotonin‐6 receptor (5‐HT6R) is a G protein‐coupled receptor and is localized almost exclusively in the central nervous system including cerebral cortex and hippocampus which are important for control of mood regulation. Masupirdine is a 5‐HT6R antagonist currently in the clinical development for the management of Alzheimer’s disease.MethodMasupirdine was evaluated for its anti‐aggressive like effects in one of the most popular preclinical aggression model i.e. Resident‐Intruder task (RIT). Male CD1 mice were used to assess the anti‐aggressive like effects in RIT. Resident animals were habituated with ovariectomized female mice and intruders were habituated socially for a period of 7 days. On day 8 and 9, basal aggression level was assessed by placing an intruder animal in the home cage of resident animal for a period of 10 min. On day 11, animals were randomized based on duration of attack and aggression level was assessed post treatment. In the control group, vehicle was administered to resident animals and for remaining groups, masupirdine was administered at doses of 1, 3 and 10 mg/kg, p.o. Additionally, masupirdine was evaluated for its effects on neurotransmitters that are involved in the modulation of behavioral and psychological symptoms using rats. Suitable statistical analysis is carried by GraphPad Prism (Version 4).ResultVehicle treated group showed almost equal duration of attack with respect to basal whereas, masupirdine significantly decreased the aggressive behavior of resident animal towards intruder at all tested doses with respect to basal. Treatment with masupirdine produced significant increase in the cortical levels of dopamine and norepinephrine. These neurochemical changes by masupirdine provide the support for anti‐aggressive behavior observed in preclinical models.ConclusionResults from the current preclinical studies indicate the promising therapeutic potential for masupirdine in the treatment of agitation/aggression.