Landipirdine

Parkinson's disease (PD) has long been seen as a disorder caused by degeneration of the dopaminergic system, leading to the classic motor manifestations of the disease. However, there is now overwhelming evidence that PD is more than a disease merely caused by dopamine depletion. It is well-known that a myriad of other neurotransmitters are affected by the disease process. One such neurotransmitter is serotonin (5-HT). 5-HT has been shown to play a role in several motor and nonmotor manifestations of PD, including tremor, cognition, depression and psychosis. 5-HT also seems to play a critical role in L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. A breadth of preclinical studies and clinical trials have been conducted that aimed at modulating the 5-HT system in order to alleviate depression, cognitive deficits, psychosis, and dyskinesia. In this Review, we summarize recent advances in the 5-HT field in PD, but with a translational emphasis. We start by presenting a novel nonhuman primate model of PD that presents with dual dopamine and 5-HT lesions. We then present preclinical and clinical data that introduce new concepts, such as the use of biased and partial agonists, as well as molecules recently introduced to the field of PD, such as eltoprazine, pimavanserin, nelotanserin, and SYN-120, to enhance therapeutic benefit while minimizing adverse events, notably on parkinsonian disability.

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.