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International Journal of Molecular... Feb 2021In the 21st century and especially during a pandemic, the diagnosis and treatment of depression is an essential part of the daily practice of many family doctors. It... (Review)
Review
In the 21st century and especially during a pandemic, the diagnosis and treatment of depression is an essential part of the daily practice of many family doctors. It mainly affects patients in the age category 15-44 years, regardless of gender. Anxiety disorders are often diagnosed in children and adolescents. Social phobias can account for up to 13% of these diagnoses. Social anxiety manifests itself in fear of negative social assessment and humiliation, which disrupts the quality of social functioning. Treatment of the above-mentioned disorders is based on psychotherapy and pharmacotherapy. Serious side effects or mortality from antidepressant drug overdose are currently rare. Recent studies indicate that paroxetine (ATC code: N06AB), belonging to the selective serotonin reuptake inhibitors, has promising therapeutic effects and is used off-label in children and adolescents. The purpose of this review is to describe the interaction of paroxetine with several molecular targets in various points of view including the basic chemical and pharmaceutical properties. The central point of the review is focused on the pharmacodynamic analysis based on the molecular mechanism of binding paroxetine to various therapeutic targets.
Topics: Animals; Antidepressive Agents, Second-Generation; Depressive Disorder; Humans; Paroxetine; Serotonin Antagonists
PubMed: 33562229
DOI: 10.3390/ijms22041662 -
Profiles of Drug Substances,... 2018Mirtazapine is one of antidepression which is used mainly in the treatment of depression, moreover, it is sometimes used in the treatment of anxiety disorders, insomnia,... (Review)
Review
Mirtazapine is one of antidepression which is used mainly in the treatment of depression, moreover, it is sometimes used in the treatment of anxiety disorders, insomnia, nausea, and vomiting, and to produce weight gain when desirable. The action of mirtazapine is an antagonist of certain adrenergic and serotonin receptors, and, furthermore, the drug is used strong as antihistamine, and it is occasionally defined as a noradrenergic and specific serotonergic antidepressant (NaSSA). The comprehensive profile of mirtazapine gives more detailed information about nomenclature, formulae, elemental analysis, and appearance. In addition, the numerous methods of drug synthesis are summarized. Also the profile covers the physicochemical properties as: the value of pK, drug solubility, melting point, X-ray powder diffraction, and analysis methods for example: (compendial, electrochemical, spectroscopic, and method of chromatographic). Besides that, the profile covered pharmacological profile and clinical pharmacokinetics in subtitle's (absorption, distribution, metabolism, and elimination). About 100 references were given as a proof of the above-mentioned studies.
Topics: Adrenergic alpha-Antagonists; Animals; Antidepressive Agents, Tricyclic; Biological Availability; Biotransformation; Drug Compounding; Drug Stability; Humans; Mianserin; Mirtazapine; Serotonin Antagonists; Technology, Pharmaceutical
PubMed: 29678261
DOI: 10.1016/bs.podrm.2018.01.002 -
ACS Chemical Neuroscience Jul 2018After the identification of the influence of serotonergic receptors in ameliorating the negative symptoms associated with schizophrenia, atypical antipsychotics were... (Review)
Review
After the identification of the influence of serotonergic receptors in ameliorating the negative symptoms associated with schizophrenia, atypical antipsychotics were developed by incorporating dopamine and serotonin antagonism. Risperidone, sold under the trade name Risperdal, was the second atypical antipsychotic developed following clozapine but quickly became a first-line treatment for acute and chronic schizophrenia because of its preferential side effect profile. Despite initial Food and Drug Administration approval 25 years ago, risperidone continues to be a fundamental treatment for schizophrenia, bipolar I disorder, and autism-related irritability. It is on the World Health Organization's List of Essential Medicines for its balance of efficacy, safety, tolerability, and cost-effectiveness. In this review, we highlight the history and importance of risperidone as an atypical antipsychotic, in addition to its chemical synthesis, manufacturing, drug metabolism and pharmacokinetics, pharmacology, structure-activity relationship, indications, and adverse effects.
Topics: Animals; Humans; Mental Disorders; Risperidone; Serotonin Antagonists
PubMed: 29695153
DOI: 10.1021/acschemneuro.8b00159 -
Expert Opinion on Pharmacotherapy Apr 2019Agomelatine is an antidepressant with unique pharmacological actions; it is both a melatonin agonist and selective serotonin antagonist. Both actions combined are... (Review)
Review
Agomelatine is an antidepressant with unique pharmacological actions; it is both a melatonin agonist and selective serotonin antagonist. Both actions combined are necessary for antidepressant efficacy. Effects on melatonin receptors enable resynchronisation of disrupted circadian rhythms with beneficial effects on sleep patterns. Areas covered: The issue of use of an antidepressant for depression co-morbid with somatic disorders is covered by the authors. A review of the literature from 2000 to August 2018 was undertaken using Scopus and Web of Science with the key words: agomelatine, depression, medical illness. Depression in Parkinson's disease, cardiovascular illness and type II diabetes is reviewed with evidence of efficacy. Bipolar depression and seasonal affective disorder may also react favourably. Agomelatine may have specific efficacy on symptoms of anhedonia. Expert opinion: Despite approval in some major jurisdictions, the drug has failed to gain registration in the United States. A defining issue may be questions about longer term efficacy: unequivocal effectiveness in placebo-controlled relapse prevention studies has not always been demonstrated. Continuation studies suggest maintenance of clinical responsiveness. A major disadvantage of the drug is its' potential hepatotoxicity and the need for repeated clinical laboratory tests.
Topics: Acetamides; Antidepressive Agents; Bipolar Disorder; Circadian Rhythm; Depression; Diabetes Mellitus, Type 2; Humans; Hypnotics and Sedatives; Seasonal Affective Disorder; Serotonin Antagonists
PubMed: 30759026
DOI: 10.1080/14656566.2019.1574747 -
Expert Opinion on Pharmacotherapy Dec 2022
Topics: Humans; Schizophrenia; Serotonin Antagonists; Antipsychotic Agents; Receptors, Serotonin
PubMed: 36250483
DOI: 10.1080/14656566.2022.2137403 -
American Journal of Health-system... Jun 2017An expanding array of options for prevention and treatment of chemotherapy-induced nausea and vomiting (CINV), including regimens containing olanzapine or recently... (Review)
Review
PURPOSE
An expanding array of options for prevention and treatment of chemotherapy-induced nausea and vomiting (CINV), including regimens containing olanzapine or recently approved neurokinin 1 (NK) receptor antagonists, are reviewed.
SUMMARY
Up to 80% of patients receiving chemotherapy have CINV. Current practice guidelines recommend that patients treated with highly emetogenic chemotherapy also receive a 3-drug antiemetic regimen initiated on the day of and continued for 3 days after chemotherapy administration, with the most commonly used 3-drug regimen consisting of an NK receptor antagonist, a 5-hydroxytryptamine type 3 (5-HT) receptor antagonist, and dexamethasone. Developments in the area of CINV management in recent years include the use of olanzapine in combination with a 5-HT antagonist and dexamethasone; Food and Drug Administration (FDA) approval of the NK receptor antagonist rolapitant, which provides a longer duration of effect than aprepitant; FDA approval of a combination product containing palonosetron and the NK receptor antagonist netupitant; and revisions of U.S. practice guidelines ending palonosetron's status as the preferred 5-HT antagonist for prevention of CINV associated with moderately or highly emetogenic chemotherapy.
CONCLUSION
Newer therapeutic options for the management of CINV are equivalent to standard-of-care regimens in terms of efficacy and toxicity. While the NK receptor antagonist rolapitant and a product combining palonosetron and netupitant have potential advantages over standard therapy in terms of convenience or pharmacologic properties, their relatively high costs must be considered.
Topics: Antiemetics; Humans; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Serotonin Antagonists; Vomiting
PubMed: 28396308
DOI: 10.2146/ajhp160227 -
Neuropharmacology May 2020The constitutive activity of different serotonin receptors (5-HTRs) toward intracellular signaling pathways has been proposed to have physiological and pathological... (Review)
Review
The constitutive activity of different serotonin receptors (5-HTRs) toward intracellular signaling pathways has been proposed to have physiological and pathological importance. Inverse agonists block the constitutive activity and can be used to probe and silence such a spontaneous activity. The constitutive activity of 5-HTRs can be observed in various heterologous systems of expression in vitro (very high for 5-HTR; very low for 5-HTR). The demonstration of the existence of this activity in native tissues and ultimately in integrative neurobiology and behavior is a real pharmacological challenge. Irrespective of the existence of mutants or polymorphisms that could alter the constitutive activity of 5-HTRs, evidence suggests that spontaneous activity of 5-HTR could impact the activity of neurobiological networks and that of 5-HTR and 5-HTR the developmental morphogenesis. Some findings exist for 5-HTR and 5-HTR in diverse though rare conditions. The existence of a constitutive activity for 5-HTR, 5-HTR, and 5-HTR is still poorly supported. When identified, the constitutive activity may differ according to brain location, state of activity (phasic in nature), and intracellular signaling pathways. A very few studies have reported aberrant constitutive activity of 5-HTRs in animal models of human diseases and patients. The purpose of this review is a critical examination of the available neuropharmacological data on the constitutive activity of 5-HTRs to determine whether this activity is an essential component of the serotonergic system transmission and it may be a possible target for CNS drug development.
Topics: Animals; Brain; Drug Inverse Agonism; Humans; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Signal Transduction
PubMed: 31958408
DOI: 10.1016/j.neuropharm.2020.107967 -
Current Diabetes Reviews 2015Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide, with reported prevalence rates ranging between 10% and 19%. Pharmacotherapy is... (Review)
Review
Major depressive disorder (MDD) is one of the most common psychiatric illnesses worldwide, with reported prevalence rates ranging between 10% and 19%. Pharmacotherapy is a first-line option for the management of MDD and, as a result, the use of antidepressants has increased 4 fold in the last 20 years. Serotonin is the most commonly dysregulated neurotransmitter in the etiology of MDD and this system is the primary focus of most medications used in the treatment of illness. Although antidepressant use in adults increases the risk of developing new onset type 2 diabetes, the mechanisms underlying this association are poorly defined. This review will focus on 1) the evidence from human and animal studies suggesting a link between the use of antidepressants that target serotonin signaling (i.e., SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitors (SARIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs)) and increased risk of diabetes, and 2) the mechanisms by which alterations in serotonin signalling by antidepressants can affect glucose homeostasis.
Topics: Animals; Antidepressive Agents; Depressive Disorder, Major; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Insulin-Secreting Cells; Risk Factors; Serotonin; Serotonin Antagonists; Selective Serotonin Reuptake Inhibitors; Weight Gain
PubMed: 25705990
DOI: 10.2174/1573399811666150223123053 -
Phytotherapy Research : PTR Oct 2022Cancer development entangles with mutation and selection for cells that progressively increase capacity for proliferation and metastasis at the cellular level. Surgery,... (Review)
Review
Cancer development entangles with mutation and selection for cells that progressively increase capacity for proliferation and metastasis at the cellular level. Surgery, chemotherapy, and radiotherapy are the standard treatments to manage several types of cancer. Chemotherapy is toxic for both normal and cancer cells and can induce unfavorable conditions, such as chemotherapy-induced nausea and vomiting (CINV), that reduce patients' quality of life. Emesis after chemotherapy is categorized into two classes acute and delayed. Since ancient times, herbal medicines have been used in various cultures to manage stomachache, vomiting, and nausea. In this manuscript, the antiemetic mechanisms of several herbal medicines and their preparations such as Zingiber officinale (5-HT, NK-1 receptor and muscarinic antagonist activity), Mentha spicata (5-HT antagonist activity), Scutellaria baicalensis (antioxidant activity), Persumac (useful in delayed phase through antioxidant, anti-inflammatory, and anti-contractile properties) and Rikkunshito (supportive in acute and delayed phase through 5-HT receptor antagonist activity) have been reviewed to show their potential effects on decreasing CINV and attract scientists attention to formulate more herbal medicine to alleviate CINV in cancer patients. However, it is crucial to say that additional high-quality investigations are required to firmly verify the clinical effectiveness and safety of each plant/compound.
Topics: Antiemetics; Antineoplastic Agents; Antioxidants; Humans; Muscarinic Antagonists; Nausea; Neoplasms; Plants, Medicinal; Quality of Life; Receptors, Neurokinin-1; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Vomiting
PubMed: 35841194
DOI: 10.1002/ptr.7563 -
ACS Chemical Neuroscience Jan 2019It is well-documented that serotonin (5-HT) exerts its pharmacological effects through a series of 5-HT receptors. The most recently identified member of this family,... (Review)
Review
It is well-documented that serotonin (5-HT) exerts its pharmacological effects through a series of 5-HT receptors. The most recently identified member of this family, 5-HT, was first identified in 1993. Over the course of the last 25 years, this receptor has been the subject of intense investigation, and it has been demonstrated that 5-HT plays an important role in a wide range of pharmacological processes. As a result of these findings, modulation of 5-HT activity has been the focus of numerous drug discovery and development programs. This review provides an overview of the roles of 5-HT in normal physiology and the therapeutic potential of this interesting drug target.
Topics: Animals; Drug Discovery; Humans; Neoplasms; Nervous System Diseases; Protein Multimerization; Protein Structure, Secondary; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists
PubMed: 30020772
DOI: 10.1021/acschemneuro.8b00283