Serotonin (5‐hydroxytryptophan [5‐HT]) is a biologically active amine expressed in platelets, in gastrointestinal (GI) cells and, to a lesser extent, in the central nervous system (CNS). This biogenic compound acts through the activation of seven 5‐HT receptors (5‐HT1‐7Rs). The 5‐HT3R is a ligand‐gated ion channel belonging to the Cys‐loop receptor family. There is a wide variety of 5‐HT3R modulators, but only receptor antagonists (known as setrons) have been used clinically for chemotherapy‐induced nausea and vomiting and irritable bowel syndrome treatment. However, since the discovery of the setrons in the mid‐1980s, a large number of studies have been published exploring new potential applications due their potency in the CNS and mild side effects. The results of these studies have revealed new potential applications, including the treatment of neuropsychiatric disorders such as schizophrenia, depression, anxiety, and drug abuse. In this review, we provide information related to therapeutic potential of 5‐HT3R antagonists on GI and neuropsychiatric disorders. The major attention is paid to the structure, function, and pharmacology of novel 5‐HT3R modulators developed over the past 10 years.

Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine. Donepezil was able to ameliorate the symptoms related to AD mainly via AChE, but also through reduction of β-amyloid burden. This review presents the overview of donepezil-related compounds as potential anti-AD drugs developed on the basis of cholinergic hypothesis to act as solely AChE and butyrylcholinesterase (BChE) inhibitors.

Dopamine is a biologically active amine synthesized in the central and peripheral nervous system. This biogenic monoamine acts by activating five types of dopamine receptors (D 1-5 Rs), which belong to the G protein-coupled receptor family. Antagonists and partial agonists of D 2 Rs are used to treat schizophrenia, Parkinson's disease, depression, and anxiety. The typical pharmacophore with high D 2 R affinity comprises four main areas, namely aromatic moiety, cyclic amine, central linker and aromatic/heteroaromatic lipophilic fragment. From the literature reviewed herein, we can conclude that 4-(2,3-dichlorophenyl), 4-(2-methoxyphenyl)-, 4-(benzo[b]thiophen-4-yl)-1-substituted piperazine, and 4-(6fluorobenzo[d]isoxazol-3-yl)piperidine moieties are critical for high D 2 R affinity. Four to six atoms chains are optimal for D 2 R affinity with 4-butoxyl as the most pronounced one. The bicyclic aromatic/heteroaromatic systems are most frequently occurring as lipophilic appendages to retain high D 2 R affinity. In this review, we provide a thorough overview of the therapeutic potential of D 2 R modulators in the treatment of the aforementioned disorders. In addition, this review summarizes current knowledge about these diseases, with a focus on the dopaminergic pathway underlying these pathologies. Major attention is paid to the structure, function, and pharmacology of novel D 2 R ligands, which have been developed in the last decade (2010-2021), and belong to the 1,4-disubstituted aromatic cyclic amine group. Due to the abundance of data,