Specific Agonists and Antagonists of Serotonergic Receptors in theTreatment of Cognitive Symptoms in Alzheimer's Disease

Abstract

In Alzheimer's disease, decreasing activity of acetylcholine and GABA in the hippocampus and prefrontal cortex are combined with cognitive deficits and with the formation of beta-amyloid. Neurotransmitter alterations in these brain regions are described, while a neurotransmitter imbalance with hypoactivity of muscarinic cholinergic, serotonergic and GABAergic neurons and hyperactivity of noradrenergic and glutamatergic neurons can be found. Serotonin including some specific receptors play an essential role in cognitive symptoms in Alzheimer's disease. Neural networks in the hippocampus and prefrontal cortex are described. Animal experiments and clinical trials about the pro-cognitive effect of 5-HT4 and 5HT7 agonists and of 5-HT3 and 5-HT6 antagonists are mentioned. The question should be investigated, whether a hybrid of a GABAA agonist and an NMDA antagonist is of a therapeutic value in mild Alzheimer's disease.

Opinion on Different Findings in Experimental and Clinical Medicine

“…Animal experiments and first clinical triasl of the cognition enhancing effect of 5-HT 4 and 5-HT 7 agonists and 5-HT 3 and 5-HT 6 antagonists are presented. The development of a hybrid combining GABA A agonists and NMDA antagonists is suggested [10].…”