Serotonergic Drugs: Agonists/Antagonists at Specific Serotonergic Subreceptors for the Treatment of Cognitive, Depressant and Psychotic Symptoms in Alzheimer’s Disease

Title:Serotonergic Drugs: Agonists/Antagonists at Specific Serotonergic Subreceptors for the Treatment of Cognitive, Depressant and Psychotic Symptoms in Alzheimer’s Disease

Volume: 22 Issue: 14

Author(s): Felix-Martin Werner and Rafael Covenas

Affiliation:

Keywords: Serotonin, brainstem, mesolimbic system, hippocampus, prefrontal cortex, cognitive functions, depression, psychosis.

Abstract: Background: Alzheimer’s disease is a neurodegenerative disease showing alterations in classical neurotransmitters, above all in the hippocampus and prefrontal/temporal cortices. In this disease, acetylcholine shows hypoactivity, noradrenaline first shows hyperactivity, and during the course of the disease an increasing hypoactivity, glutamate shows hyperactivity and excitotoxicity and GABA shows hypoactivity. In post-mortem studies, serotonin levels and the number of specific serotonergic subreceptors, for example 5-HT_1B receptors, decreased. Methods: We summarized the alterations of classical neurotransmitters in the brain regions involved in cognitive, depressive and psychotic symptoms in Alzheimer’s disease. Starting from these neurotransmitter alterations, we describe neural networks including specific serotonergic subreceptors in the involved brain regions. Results: In the hippocampus and prefrontal cortex, serotonin levels are associated with cognitive functions, whereas in the brainstem serotonin levels are related with affective symptoms. Psychotic symptoms which can occur in patients with Alzheimer’s disease are associated with dopamine and serotonin hyperactivity in the mesolimbic system and hippocampus. The interaction between classical neurotransmitters and their specific subreceptors is shown in different brain areas. Conclusion: In clinical trials, the therapeutic effects of 5-HT₄, 5-HT₇ agonists and 5-HT₃, 5-HT₆ antagonists have been examined to improve cognitive symptoms in Alzheimer’s disease. In these trials, 5-HT₄ agonists and 5-HT₄ antagonists showed a significant better effect in improving cognitive functions than placebo. The effect of such drugs on the formation of amyloid plaques is also examined. The appropriate use of antidepressant and antipsychotic drugs with an agonism or antagonism at specific serotonergic subreceptors is pointed out. Serotonin-selective antidepressant drugs significantly improve depressant symptoms and daily activities in Alzheimer patients and they are used to treat aggressive behaviour. Among the second-generations antipsychotic drugs (D₂ and 5-HT_2A antagonists), drugs with a favorable metabolic profile should be used.

Cite this article as:

Werner Felix-Martin and Covenas Rafael, Serotonergic Drugs: Agonists/Antagonists at Specific Serotonergic Subreceptors for the Treatment of Cognitive, Depressant and Psychotic Symptoms in Alzheimer’s Disease, Current Pharmaceutical Design 2016; 22 (14) . https://dx.doi.org/10.2174/1381612822666160127113524