Efficacy and Safety of Sertindole in Schizophrenia

Zoccali, Rocco Antonio; Bruno, Antonio; Muscatello, Maria Rosaria Anna

doi:10.1097/jcp.0000000000000305

Cited by 11 publications

(15 citation statements)

References 81 publications

(93 reference statements)

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“…Sertindole is an indole derivative with a high affinity for dopamine D 2 , serotonin 5-HT 2A and 5-HT 2C , and α 1 adrenergic receptors [ 120 ]. It has also some affinity for histamine H 1 and muscarinic receptors.…”

Section: Classical Approaches To Treat Schizophreniamentioning

confidence: 99%

Current Concepts and Treatments of Schizophrenia

2018

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Schizophrenia is a debilitating mental illness which involves three groups of symptoms, i.e., positive, negative and cognitive, and has major public health implications. According to various sources, it affects up to 1% of the population. The pathomechanism of schizophrenia is not fully understood and current antipsychotics are characterized by severe limitations. Firstly, these treatments are efficient for about half of patients only. Secondly, they ameliorate mainly positive symptoms (e.g., hallucinations and thought disorders which are the core of the disease) but negative (e.g., flat affect and social withdrawal) and cognitive (e.g., learning and attention disorders) symptoms remain untreated. Thirdly, they involve severe neurological and metabolic side effects and may lead to sexual dysfunction or agranulocytosis (clozapine). It is generally agreed that the interactions of antipsychotics with various neurotransmitter receptors are responsible for their effects to treat schizophrenia symptoms. In particular, several G protein-coupled receptors (GPCRs), mainly dopamine, serotonin and adrenaline receptors, are traditional molecular targets for antipsychotics. Comprehensive research on GPCRs resulted in the exploration of novel important signaling mechanisms of GPCRs which are crucial for drug discovery: intentionally non-selective multi-target compounds, allosteric modulators, functionally selective compounds and receptor oligomerization. In this review, we cover current hypotheses of schizophrenia, involving different neurotransmitter systems, discuss available treatments and present novel concepts in schizophrenia and its treatment, involving mainly novel mechanisms of GPCRs signaling.

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Section: Classical Approaches To Treat Schizophreniamentioning

confidence: 99%

Current Concepts and Treatments of Schizophrenia

2018

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“…This drug was authorized and introduced into the market in 1996 but was voluntarily withdrawn in 1998 after numerous cardiac adverse effects were reported . Various studies revealed that increased drug concentration could lead to increased risk of QTc prolongation. , However, after a reevaluation of its risks and benefits, sertindole was reintroduced into the European market in 2005, and the drug is currently available in several countries …”

Section: Fluorine-containing Pharmaceuticals Withdrawn From the Marketmentioning

confidence: 99%

“…313,314 However, after a reevaluation of its risks and benefits, sertindole was reintroduced into the European market in 2005, and the drug is currently available in several countries. 315 6.1.2. Aromatic Trifluoromethyl-Substituted Compounds.…”

Section: Fluorine-containing Pharmaceuticals Withdrawn From the Marketmentioning

confidence: 99%

Chemical Aspects of Human and Environmental Overload with Fluorine

et al. 2021

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Over the last 100–120 years, due to the ever-increasing importance of fluorine-containing compounds in modern technology and daily life, the explosive development of the fluorochemical industry led to an enormous increase of emission of fluoride ions into the biosphere. This made it more and more important to understand the biological activities, metabolism, degradation, and possible environmental hazards of such substances. This comprehensive and critical review focuses on the effects of fluoride ions and organofluorine compounds (mainly pharmaceuticals and agrochemicals) on human health and the environment. To give a better overview, various connected topics are also discussed: reasons and trends of the advance of fluorine-containing pharmaceuticals and agrochemicals, metabolism of fluorinated drugs, withdrawn fluorinated drugs, natural sources of organic and inorganic fluorine compounds in the environment (including the biosphere), sources of fluoride intake, and finally biomarkers of fluoride exposure.

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“…Indole ring is present in a great variety of biologically relevant compounds, from the amino acid tryptophan to the hormone melatonin and the neurotransmitter serotonin as well as complex plant secondary metabolites such as vincristine and reserpine, used as chemotherapeutic agents [1] and in hypertension management. [2] Furthermore, the indole ring has attracted considerable attention as scaffold for the development of a great variety of drugs, such as sumatriptan, [3] tadalafil, [4] sertindole, [5] bazedoxifene, [6] just to cite a few, and many others are still under investigation. [7] A large variety of indole synthesis have been established (a selection is reported in Scheme 1).…”

Section: Introductionmentioning

confidence: 99%