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Journal of the American Academy of... Sep 2023Antipsychotic-induced hyperprolactinemia is common in children and adolescents, but this quotidian presence in our clinics should neither reassure us nor make us...
Antipsychotic-induced hyperprolactinemia is common in children and adolescents, but this quotidian presence in our clinics should neither reassure us nor make us complacent. The report by Koch and colleagues stands out against the landscape of trials describing the adverse effects of psychotropic medications in youth. It goes beyond the typical examination of adverse effects in most clinical trials. The authors followed children and adolescents aged 4 to 17 years who were dopamine-serotonin receptor antagonist naive (≤1-week exposure) or free, and serially evaluated not only serum prolactin concentrations but medication concentrations and side effects for 12 weeks after participants began aripiprazole, olanzapine, quetiapine, or risperidone. This report provides insights into the temporal course of adverse effects, examines differential tolerability among dopamine-serotonin receptor antagonists, links specific adverse effects-galactorrhea, decreased libido, and erectile dysfunction-with prolactin concentrations in youth, and focuses on the clinical aspects of hyperprolactinemia and related adverse effects in children and adolescents.
Topics: Male; Female; Adolescent; Child; Humans; Antipsychotic Agents; Hyperprolactinemia; Prolactin; Dopamine; Risperidone; Aripiprazole
PubMed: 37172820
DOI: 10.1016/j.jaac.2023.05.003 -
Neuropsychopharmacology : Official... Jun 2023Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the...
Psilocybin has been shown to improve symptoms of depression and anxiety when combined with psychotherapy or other clinician-guided interventions. To understand the neural basis for this pattern of clinical efficacy, experimental and conceptual approaches that are different than traditional laboratory models of anxiety and depression are needed. A potential novel mechanism is that acute psilocybin improves cognitive flexibility, which then enhances the impact of clinician-assisted interventions. Consistent with this idea, we find that acute psilocybin robustly improves cognitive flexibility in male and female rats using a task where animals switched between previously learned strategies in response to uncued changes in the environment. Psilocybin did not influence Pavlovian reversal learning, suggesting that its cognitive effects are selective to enhanced switching between previously learned behavioral strategies. The serotonin (5HT) 2 A receptor antagonist ketanserin blocked psilocybin's effect on set-shifting, while a 5HT2C-selective antagonist did not. Ketanserin alone also improved set-shifting performance, suggesting a complex relationship between psilocybin's pharmacology and its impact on flexibility. Further, the psychedelic drug 2,5-Dimethoxy-4-iodoamphetamine (DOI) impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics. We conclude that the acute impact of psilocybin on cognitive flexibility provides a useful behavioral model to investigate its neuronal effects relevant to its positive clinical outcome.
Topics: Male; Female; Animals; Rats; Psilocybin; Ketanserin; Hallucinogens; Anxiety; Serotonin 5-HT2 Receptor Antagonists; Serotonin; Cognition
PubMed: 36807609
DOI: 10.1038/s41386-023-01545-z -
Expert Opinion on Pharmacotherapy Dec 2022
Topics: Humans; Schizophrenia; Serotonin Antagonists; Antipsychotic Agents; Receptors, Serotonin
PubMed: 36250483
DOI: 10.1080/14656566.2022.2137403 -
Best Practice & Research. Clinical... Dec 2020Postoperative nausea and vomiting (PONV) and post-discharge nausea and vomiting (PDNV) are frequent unpleasant complaints that patients and clinicians report after... (Review)
Review
Postoperative nausea and vomiting (PONV) and post-discharge nausea and vomiting (PDNV) are frequent unpleasant complaints that patients and clinicians report after surgery. PONV and PDNV have been associated with postoperative complications and hospital discharge delays. Despite the extensive evidence describing the use of several regimens in different surgical populations, the ideal regimen has not been established. Several antiemetic drugs have been evaluated in more than 1000 clinical controlled trials for management of this complex emetogenic pathway, including the 5-hydroxytryptamine (5-HT) receptor antagonists, dopamine receptor antagonists, neurokinin-type receptor antagonists, antihistaminics, anticholinergics, and corticosteroids, with the 5-HT receptor antagonists being the most commonly used for PONV prophylaxis. Because of the complex emetogenic pathway and multifactorial etiology of PONV, a multimodal approach using two or more drugs that act at different neuro-receptor sites is suggested in patients with one or more risk factors to successfully address PONV and reduce its incidence. Nevertheless, the most studied regimens in randomized clinical trials (RCTs) are the combination of serotonin 5-HT3 receptor antagonists with dexamethasone or dopamine receptor antagonists (droperidol). Therefore, the safest and more effective combination regimen appears to be the use of serotonin 5-HT3 receptor antagonist antiemetic drugs with dexamethasone.
Topics: Aftercare; Antiemetics; Dopamine Antagonists; Drug Therapy, Combination; Histamine Antagonists; Humans; Meta-Analysis as Topic; Patient Discharge; Postoperative Nausea and Vomiting; Risk Factors; Serotonin 5-HT3 Receptor Antagonists; Sex Factors; Systematic Reviews as Topic
PubMed: 33288120
DOI: 10.1016/j.bpa.2020.10.009 -
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 -
Biochimica Et Biophysica Acta.... Jun 2020G protein-coupled receptors (GPCRs) constitute the largest superfamily of membrane proteins in higher eukaryotes, and facilitate information transfer from the...
G protein-coupled receptors (GPCRs) constitute the largest superfamily of membrane proteins in higher eukaryotes, and facilitate information transfer from the extracellular environment to the cellular interior upon activation by ligands. Their role in diverse signaling processes makes them an attractive choice as drug targets. GPCRs are coupled to heterotrimeric G-proteins which represent an important interface through which signal transduction occurs across the plasma membrane upon activation by ligands. To obtain further insight into the molecular details of interaction of G-proteins with GPCRs, in this work, we explored the selectivity of binding of specific agonists and antagonists to the serotonin receptor under conditions of progressive G-protein inactivation. The serotonin receptor is an important neurotransmitter receptor belonging to the GPCR family and is a popular drug target. By use of a number of agents to inactivate G-proteins, we show here that the serotonin receptor displays differential discrimination between agonist and antagonist binding. Our results show a reduction in binding sites of the receptor upon treatment with G-protein inactivating agents. In addition, G-protein coupling efficiency was enhanced when G-proteins were inactivated using urea and alkaline pH. We envision that our results could be useful in achieving multiple signaling states of the receptor by fine tuning the conditions of G-protein inactivation and in structural biology of GPCRs bound to specific ligands.
Topics: Binding Sites; Drug Discovery; GTP-Binding Proteins; Hydrogen-Ion Concentration; Protein Binding; Receptor, Serotonin, 5-HT1A; Receptors, G-Protein-Coupled; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists; Urea
PubMed: 32156647
DOI: 10.1016/j.bbamem.2020.183265 -
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 -
Neuropharmacology Nov 2020Targeting the serotonin (5-HT) system is no simple task: there are at least 15 5-HT receptors, in addition to a number of transporters and metabolizing enzymes. Multiple... (Review)
Review
Targeting the serotonin (5-HT) system is no simple task: there are at least 15 5-HT receptors, in addition to a number of transporters and metabolizing enzymes. Multiple 5-HT receptor variants exist due to genetic variations and/or post translational modifications, splice variants or editing variants. Some receptors may form homo and heteromers. The 5-HT system is targeted by multiple drugs to treat a variety of diseases. Given the homology amongst the 5-HT and neighbouring receptor classes, only few drugs are actually selective for a single target. In fact, many 5-HT drugs act on a combination of targets, i.e. several receptors and/or transporters or enzymes. For instance, a number of antidepressants or antipsychotics act on 5-HT and other transmitter systems. Recently developed drugs may show target selectivity by design, based on the current state of knowledge, whereas many older compounds hit multiple targets since they were developed using phenotypic screens, as was done well into the 1980's. Ergot analogues, antipsychotics or antidepressants, fall into this category. As our knowledge developed over the last 25-30 years, some targets have very well-defined liabilities: for instance, 5HT or 5-HT receptor agonists, will produce valvulopathies or hallucinations, respectively, whereas 5-HT receptor antagonists, may lead to constipation. This short review will be limited in scope as there are multiple targets and even more compounds to discuss. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Drug Delivery Systems; Humans; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Serotonin Plasma Membrane Transport Proteins; Serotonin Receptor Agonists; Serotonin Syndrome; Selective Serotonin Reuptake Inhibitors
PubMed: 32805212
DOI: 10.1016/j.neuropharm.2020.108233 -
Fertility and Sterility Sep 2021Primum non nocere. As physicians, our goal is to treat illnesses and alleviate suffering; however, in doing so, we can generate new problems in a game of medical... (Review)
Review
Primum non nocere. As physicians, our goal is to treat illnesses and alleviate suffering; however, in doing so, we can generate new problems in a game of medical whack-a-mole. For some patients, certain consequences or side effects are tolerable, while others may believe they have no alternative. For a male patient with infertility, a thorough history is imperative to elucidate whether the patient has been or is currently being exposed to medications that will harm libido, spermatogenesis, ejaculation, or the hypothalamic-pituitary-testosterone axis. This article will review the most common medications causing iatrogenic male infertility as well as options to minimize or even reverse their impact.
Topics: 5-alpha Reductase Inhibitors; Analgesics, Opioid; Androgen Antagonists; Animals; Antineoplastic Agents; Fertility; Humans; Infertility, Male; Male; Radiotherapy; Risk Factors; Serotonin Antagonists; Testosterone
PubMed: 34462096
DOI: 10.1016/j.fertnstert.2021.07.1202 -
American Journal of Therapeutics 2019
Topics: Bipolar Disorder; Delirium; Dopamine D2 Receptor Antagonists; Humans; Lurasidone Hydrochloride; Male; Middle Aged; Psychiatric Status Rating Scales; Serotonin 5-HT2 Receptor Antagonists
PubMed: 30839323
DOI: 10.1097/MJT.0000000000000959