<p>Serotonin Type 6 and 7 Receptors as a Novel Therapeutic Target for the Treatment of Schizophrenia</p>

Abstract

Schizophrenia is a serious disease of the central nervous system that affects a person’s ability to think, feel and behave clearly. Even though the pathophysiological hypothesis of the disease is not clearly understood, dysfunction of dopamine, glutamate, serotonin and other neurotransmitters is widely believed to be involved. Serotonin within the synaptic vesicles functions as neurotransmitter and neurohormone in regulation of emotion, learning, memory, hormone release, cognition and motor function. Dysfunction of normal brain activity of serotonin is associated with schizophrenia. The role of serotonin 6 and 7 receptors in schizophrenia, interaction with neurotransmitters and the effect of drugs on those receptors in schizophrenia are the goal of this review. The aim of this review was to provide information for researchers and other scholars to identify the possible intervention points in the management of schizophrenia. The serotonin 6 and 7 receptors are associated with schizophrenia via modulating cyclic adenosine monophosphate, regulation of Fyn kinase and induction of structural plasticity. The above modulatory effects affect cholinergic, dopaminergic, glutamatergic, adrenergic and GABAergic systems. Recently, diverse numbers of selective agonist and antagonist ligands were developed for both receptors. SGS-518, ABT-354, Lu AE58054, SB-742,457, S-518, AVN-211, AVN-322, SYN-114 and SYN-120 are serotonin 6 receptor antagonists and aripiprazole-controlled release serotonin 7 receptor agonists under clinical trial for schizophrenia. Thus, research on novel drugs that act on serotonin 6 and 7 receptors likely facilitates the intervention into schizophrenia patients seeking better quality of life in the future.

Low Basicity as a Characteristic for Atypical Ligands of Serotonin Receptor 5-HT2

“…Serotonin receptors (5-HTRs) are a group of proteins extensively examined by academic and commercial researchers, due to their vital roles, which they play in the organism, constituting thus important drug targets for a wide range of disorders [1,2]. Their endogenous ligand, serotonin, modulates numerous processes, such as mood, perception, reward, anger, aggression, appetite, memory, sexuality, attention, among others; however, it also controls other, non-neuropsychological processes, such as vasoconstriction, digestion, muscle contraction, and inflammatory mediation [1,[3][4][5][6][7].…”

“…The current classification of serotonin receptors group them into seven classes (5-HT 1-7 ) with a total of 14 members. Except for 5-HT 3 R which is a ligand-gated ion channel, serotonin receptor actions are mediated via G proteins, which makes them representatives of the G protein-coupled receptors (GPCRs) [2,15,16]. All metabotropic 5-HTRs share the same architecture of seven transmembrane domains (TMDs) and one intramembrane helix 8 (H8), which are connected by intra-and extracellular loops (ICLs and ECLs, respectively).…”

Genetic polymorphism and neuroanatomical changes in schizophrenia

“…Dysfunction of serotonin pathways has been associated with psychiatric disorders. In schizophrenia, high levels of serotonin have been observed in areas of the anterior cingulate cortex and in the dorsolateral frontal lobe, being associated with the appearance of positive symptoms [ 105 ]. The serotonin hypothesis emerged after studies showed a decrease in hallucinatory behavior and a slowing of the progression of the disorder when drugs that blocked 5-HT2A receptors were administered.…”

Association between the loudness dependence of auditory evoked potentials and age in patients with schizophrenia and depression

“… 5 However, the pathological complexity underlying these changes in serotonin neurotransmission is not clearly understood. 6 – 9 MDD is a heterogeneous disorder because only 30% to 40% of patients respond to antidepressants. 10 , 11 SCZ also shows heterogeneity, and the understanding of the serotonergic neuropathological effects on the brain is unclear.…”