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Brain and Behavior Jun 2023Sydenham's chorea (SC), prevalent in developing countries and occasionally affecting developed ones, poses a clinical challenge due to the lack of systematic guidelines... (Review)
Review
INTRODUCTION
Sydenham's chorea (SC), prevalent in developing countries and occasionally affecting developed ones, poses a clinical challenge due to the lack of systematic guidelines for diagnosis and treatment. Resulting from Group A Beta-Hemolytic Streptococcus infection, SC presents various symptoms. This review aims to collect and evaluate available data on SC management to propose a cohesive treatment plan.
METHODS
We searched PubMed, the Cochrane Library, Google Scholar, and ClinicalTrials.gov for literature on SC management from inception until 24th July 2022. Studies were screened by titles and abstracts. Cochrane Collaboration's Risk of Bias tool (RoB-1) assessed Randomized Controlled Trials, while the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool evaluated nonrandomized studies.
RESULTS
The review includes 11 articles assessing 579 patients. Excluding one study with 229 patients, of the remaining 550 patients, 338 (61.5%) were females. Treatments used were dopamine antagonists in 118 patients, antiepileptics in 198, corticosteroids in 134, IVIG in 7, and PE in 8 patients. Dopamine antagonists, particularly haloperidol, were the primary treatment choice, while valproic acid (VPA) was favored among antiepileptics. Prednisolone, a corticosteroid, showed promising results with weight gain as the only side-effect. Our review emphasizes the importance of immunomodulators in SC, contrasting previous literature.
CONCLUSION
Despite limitations, dopamine antagonists can serve as first-line agents in SC management, followed by antiepileptics. The role of immunomodulators warrants further investigation for conclusive recommendations.
Topics: Female; Humans; Male; Chorea; Anticonvulsants; Valproic Acid; Haloperidol; Dopamine Antagonists
PubMed: 37150977
DOI: 10.1002/brb3.3035 -
Seminars in Cancer Biology Jan 2021The recent development of high throughput compound screening has allowed drug repurposing to emerge as an effective avenue for discovering novel treatments for cancer.... (Review)
Review
The recent development of high throughput compound screening has allowed drug repurposing to emerge as an effective avenue for discovering novel treatments for cancer. FDA-approved antipsychotic drugs fluspirilene, penfluridol, and pimozide are clinically used for the treatment of psychotic disorders, primarily schizophrenia. These compounds, belong to diphenylbutylpiperidine class of antipsychotic drugs, are the potent inhibitors of dopamine D2 receptor and calcium channel. A correlation has been found that patients treated for schizophrenia have lower incidences of certain types of cancer, such as respiratory, prostate, and bladder cancers. These compounds have also been shown to inhibit cancer proliferation in a variety of cancer cells, including melanoma, lung carcinoma, breast cancer, pancreatic cancer, glioma, and prostate cancer, among others. Antipsychotic drugs induce apoptosis and suppress metastasis in in vitro and in vivo models through mechanisms involving p53, STAT3, STAT5, protein phosphatase 2A, cholesterol homeostasis, integrins, autophagy, USP1, wnt/β-catenin signaling, and DNA repair. Additionally, pre-clinical evidence suggests that penfluridol and pimozide act synergistically with existing chemotherapeutic agents, such as dasatinib, temozolomide, and cisplatin. Some studies have also reported that the cytotoxic activity of the antipsychotics is selective for dividing cells. Based on this growing body of evidence and the availability and previous FDA-approval of the drugs, the compounds appear to be promising anti-cancer agents.
Topics: Animals; Antineoplastic Agents; Antipsychotic Agents; Butyrophenones; Drug Discovery; Drug Repositioning; Humans; Neoplasms; Piperidines
PubMed: 31618686
DOI: 10.1016/j.semcancer.2019.10.007 -
The Journal of Neuroscience : the... May 2022Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion...
Emotion recognition abilities are fundamental to our everyday social interaction. A large number of clinical populations show impairments in this domain, with emotion recognition atypicalities being particularly prevalent among disorders exhibiting a dopamine system disruption (e.g., Parkinson's disease). Although this suggests a role for dopamine in emotion recognition, studies employing dopamine manipulation in healthy volunteers have exhibited mixed neural findings and no behavioral modulation. Interestingly, while a dependence of dopaminergic drug effects on individual baseline dopamine function has been well established in other cognitive domains, the emotion recognition literature so far has failed to account for these possible interindividual differences. The present within-subjects study therefore tested the effects of the dopamine D2 antagonist haloperidol on emotion recognition from dynamic, whole-body stimuli while accounting for interindividual differences in baseline dopamine. A total of 33 healthy male and female adults rated emotional point-light walkers (PLWs) once after ingestion of 2.5 mg haloperidol and once after placebo. To evaluate potential mechanistic pathways of the dopaminergic modulation of emotion recognition, participants also performed motoric and counting-based indices of temporal processing. Confirming our hypotheses, effects of haloperidol on emotion recognition depended on baseline dopamine function, where individuals with low baseline dopamine showed enhanced, and those with high baseline dopamine decreased emotion recognition. Drug effects on emotion recognition were related to drug effects on movement-based and explicit timing mechanisms, indicating possible mediating effects of temporal processing. Results highlight the need for future studies to account for baseline dopamine and suggest putative mechanisms underlying the dopaminergic modulation of emotion recognition. A high prevalence of emotion recognition difficulties among clinical conditions where the dopamine system is affected suggests an involvement of dopamine in emotion recognition processes. However, previous psychopharmacological studies seeking to confirm this role in healthy volunteers thus far have failed to establish whether dopamine affects emotion recognition and lack mechanistic insights. The present study uncovered effects of dopamine on emotion recognition in healthy individuals by controlling for interindividual differences in baseline dopamine function and investigated potential mechanistic pathways via which dopamine may modulate emotion recognition. Our findings suggest that dopamine may influence emotion recognition via its effects on temporal processing, providing new directions for future research on typical and atypical emotion recognition.
Topics: Adult; Dopamine; Dopamine D2 Receptor Antagonists; Emotions; Female; Haloperidol; Humans; Male; Perception
PubMed: 35501156
DOI: 10.1523/JNEUROSCI.2364-21.2022 -
Frontiers in Immunology 2020The spread of the novel human respiratory coronavirus (SARS-CoV-2) is a global public health emergency. There is no known successful treatment as of this time, and there... (Review)
Review
The spread of the novel human respiratory coronavirus (SARS-CoV-2) is a global public health emergency. There is no known successful treatment as of this time, and there is a need for medical options to mitigate this current epidemic. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and is primarily trophic for the lower and upper respiratory tract. A number of current studies on COVID-19 have demonstrated the substantial increase in pro-inflammatory factors in the lungs during infection. The virus is also documented in the central nervous system and, particularly in the brainstem, which plays a key role in respiratory and cardiovascular function. Currently, there are few antiviral approaches, and several alternative drugs are under investigation. Two of these are Idelalisib and Ebastine, already proposed as preventive strategies in airways and allergic diseases. The interesting and evolving potential of phosphoinositide 3-kinase δ (PI3Kδ) inhibitors, together with Ebastine, lies in their ability to suppress the release of pro-inflammatory cytokines, such as IL-1β, IL-8, IL-6, and TNF-α, by T cells. This may represent an optional therapeutic choice for COVID-19 to reduce inflammatory reactions and mortality, enabling patients to recover faster. This concise communication aims to provide new potential therapeutic targets capable of mitigating and alleviating SARS-CoV-2 pandemic infection.
Topics: Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antiviral Agents; Betacoronavirus; Butyrophenones; COVID-19; Class I Phosphatidylinositol 3-Kinases; Coronavirus Infections; Drug Repositioning; Humans; Inflammation; Interleukin-6; Molecular Targeted Therapy; Pandemics; Peptidyl-Dipeptidase A; Piperidines; Pneumonia, Viral; Purines; Quinazolinones; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32973818
DOI: 10.3389/fimmu.2020.02094 -
Pharmacological Research Aug 2023Schizophrenia (SCZ) is a severe psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive deficits. Current antipsychotic treatment in...
Schizophrenia (SCZ) is a severe psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive deficits. Current antipsychotic treatment in SCZ improves positive symptoms but has major side effects and little impact on negative symptoms and cognitive impairment. The pathoetiology of SCZ remains unclear, but is known to involve small GTPase signaling. Rho kinase, an effector of small GTPase Rho, is highly expressed in the brain and plays a major role in neurite elongation and neuronal architecture. This study used a touchscreen-based visual discrimination (VD) task to investigate the effects of Rho kinase inhibitors on cognitive impairment in a methamphetamine (METH)-treated male mouse model of SCZ. Systemic injection of the Rho kinase inhibitor fasudil dose-dependently ameliorated METH-induced VD impairment. Fasudil also significantly suppressed the increase in the number of c-Fos-positive cells in the infralimbic medial prefrontal cortex (infralimbic mPFC) and dorsomedial striatum (DMS) following METH treatment. Bilateral microinjections of Y-27632, another Rho kinase inhibitor, into the infralimbic mPFC or DMS significantly ameliorated METH-induced VD impairment. Two proteins downstream of Rho kinase, myosin phosphatase-targeting subunit 1 (MYPT1; Thr696) and myosin light chain kinase 2 (MLC2; Thr18/Ser19), exhibited increased phosphorylation in the infralimbic mPFC and DMS, respectively, after METH treatment, and fasudil inhibited these increases. Oral administration of haloperidol and fasudil ameliorated METH-induced VD impairment, while clozapine had little effect. Oral administration of haloperidol and clozapine suppressed METH-induced hyperactivity, but fasudil had no effect. These results suggest that METH activates Rho kinase in the infralimbic mPFC and DMS, which leads to cognitive impairment in male mice. Rho kinase inhibitors ameliorate METH-induced cognitive impairment, perhaps via the cortico-striatal circuit.
Topics: Animals; Male; Mice; Clozapine; Cognitive Dysfunction; Haloperidol; Methamphetamine; Monomeric GTP-Binding Proteins; rho-Associated Kinases; Schizophrenia; Protein Kinase Inhibitors
PubMed: 37390993
DOI: 10.1016/j.phrs.2023.106838 -
Deutsches Arzteblatt International Jun 2019Psychomotor agitation and aggressiveness in the context of mental illnessare medical emergencies. In a survey of six German psychiatric hospitals, 1.7 to 5 aggressive... (Review)
Review
BACKGROUND
Psychomotor agitation and aggressiveness in the context of mental illnessare medical emergencies. In a survey of six German psychiatric hospitals, 1.7 to 5 aggressive attacks per patient-year were reported. If talking to the patient has no calming effect, intervention with drugs is required. In this article, we review the evidence on tranquilizing drugs and discuss clinically relevant ethical and practical questions, e.g., with respect to involuntary medication.
METHODS
This review is based on pertinent articles retrieved by a selective search in MEDLINE, supplemented by a reference search.
RESULTS
The evidence for the treatment of psychomotor agitation with antipsychotic drugs and benzodiazepines is relatively good. Randomized, controlled trials and a number of Cochrane reviews are available. These publications, however, contain data only on patients who were able to give informed consent. Their findings are often not applicable to real-life emergencies, e.g., when the patient is intoxicated with alcohol or suffers from a pre-existing disease. Haloperidol has a relatively weak effect on aggression when given alone and can also cause side effects such as early dyskinesia and epileptic seizures. It should, therefore, no longer be used as monotherapy. On the other hand, haloperidol combined with benzodiazepines or promethazine and monotherapy with lorazepam, olanzapine, ziprasidone, or aripiprazole intramuscular are effective options for the treatment of aggressive psychomotor agitation.
CONCLUSION
All of these drugs, if accepted by the patient, can also have an additional, beneficial placebo effect, with the patient calming down more rapidly than could be explained on pharmacological grounds alone. It is, therefore, important in emergencies (as at other times) for the patient to be involved in treatment decisions to the greatest possible extent.
Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Haloperidol; Humans; Psychomotor Agitation; Psychotic Disorders
PubMed: 31431244
DOI: 10.3238/arztebl.2019.0445 -
BMJ Case Reports Oct 2021A 28-year-old woman presenting with agitation and mania with psychotic features developed symptoms of isolated lingual dystonia shortly after the initiation of a...
A 28-year-old woman presenting with agitation and mania with psychotic features developed symptoms of isolated lingual dystonia shortly after the initiation of a haloperidol concentrate regimen.
Topics: Adult; Dystonia; Dystonic Disorders; Female; Haloperidol; Humans
PubMed: 34610953
DOI: 10.1136/bcr-2021-242272 -
BMC Psychiatry Jul 2023Abnormal activation of microglia is involved in the pathogenesis of schizophrenia. Minocycline and antipsychotics have been reported to be effective in inhibiting the...
BACKGROUND
Abnormal activation of microglia is involved in the pathogenesis of schizophrenia. Minocycline and antipsychotics have been reported to be effective in inhibiting the activation of microglia and thus alleviating the negative symptoms of patients with schizophrenia. However, the specific molecular mechanism by which minocycline and antipsychotics inhibit microglial activation is not clear. In this study, we aimed to explore the molecular mechanism of treatment effect of minocycline and antipsychotics on schizophrenia.
METHODS
Microglia cells were activated by lipopolysaccharide (LPS) and further treated with minocycline, haloperidol, and risperidone. Then cell morphology, specific marker, cytokines, and nitric oxide production process, and the proteins in related molecular signaling pathways in LPS-activated microglia were compared among groups.
RESULTS
The study found that minocycline, risperidone, and haloperidol significantly inhibited morphological changes and reduced the expression of OX-42 protein induced by LPS. Minocycline significantly decreased the production of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-1beta (IL-1β). Risperidone also showed significant decrease in the production of IL-6 and TNF-α, while haloperidol only showed significant decrease in the production of IL-6. Minocycline, risperidone, and haloperidol were found to significantly inhibit nitric oxide (NO) expression, but had no effect on inducible nitric oxide synthase (iNOS) expression. Both minocycline and risperidone were effective in decreasing the activity of c‑Jun N‑terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in the mitogen-activated protein kinases (MAPKs) signal pathway. Additionally, minocycline and risperidone were found to increase the activity of phosphorylated-p38. In contrast, haloperidol only suppressed the activity of ERK. Minocycline also suppressed the activation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), while risperidone and haloperidol only suppressed the activation of STAT3.
CONCLUSIONS
The results demonstrated that minocycline and risperidone exert stronger anti-inflammatory and neuroprotective effects stronger than haloperidol, through MAPKs and Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathways in BV2 cells stimulated with LPS, revealing the underlying mechanisms of minocycline and atypical antipsychotics in the treatment of negative schizophrenia symptoms.
Topics: Humans; Antipsychotic Agents; Microglia; Lipopolysaccharides; Minocycline; Haloperidol; Risperidone; Tumor Necrosis Factor-alpha; Interleukin-6; Nitric Oxide; Signal Transduction; Nitric Oxide Synthase Type II
PubMed: 37464316
DOI: 10.1186/s12888-023-05014-1 -
Communications Biology Jun 2021There is a continual need to develop new therapies for neuropsychiatric disorders such as Schizophrenia, and identifying the underlying molecular processes remains...
There is a continual need to develop new therapies for neuropsychiatric disorders such as Schizophrenia, and identifying the underlying molecular processes remains challenging. Chadha et al. recently discovered a potential role for mTOR kinase activity disruption in Schizophrenia and further uncover the precise pathomechanism. Their study sheds further light on the role of mTOR in Schizophrenia and could inform the development of future therapeutic strategies for the condition.
Topics: Animals; Antipsychotic Agents; Brain; Drug Discovery; Haloperidol; Humans; Molecular Targeted Therapy; Schizophrenia; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 34112930
DOI: 10.1038/s42003-021-02270-3 -
Sao Paulo Medical Journal = Revista... 2023Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics...
BACKGROUND
Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics and less frequently with atypical or second-generation antipsychotics. The diagnosis relies on both clinical and laboratory criteria, with other organic and psychiatric conditions being ruled out.
CASE REPORT
A 39-year-old female patient, who is institutionalized and completely dependent, has a medical history of recurrent urinary infections and colonization by carbapenem-resistant Klebsiella pneumoniae. Her regular medication regimen included sertraline, valproic acid, quetiapine, risperidone, lorazepam, diazepam, haloperidol, baclofen, and fentanyl. The patient began experiencing dyspnea. Upon physical examination, she exhibited hypotension and a diminished vesicular murmur at the right base during pulmonary auscultation. Initially, after hospitalization, she developed high febrile peaks associated with hemodynamic instability, prompting the initiation of antibiotic treatment. Despite this, her fever persisted without an increase in blood inflammatory parameters, and she developed purulent sputum, necessitating antibiotherapy escalation. The seventh day of hospitalization showed no improvement in symptoms, suggesting NNMS as a differential diagnosis. All antipsychotic and sedative drugs, as well as antibiotherapy, were discontinued, after which the patient showed significant clinical improvement.
CONCLUSION
Antipsychotic agents are commonly employed to manage behavioral changes linked to various disorders. However, their severe side effects necessitate a high degree of vigilance, the cessation of all medications, and the implementation of supportive care measures. A prompt and accurate diagnosis of NMS is crucial to alleviating the severe, prolonged morbidity and potential mortality associated with this syndrome.
Topics: Female; Humans; Adult; Antipsychotic Agents; Haloperidol; Quetiapine Fumarate; Risperidone; Neuroleptic Malignant Syndrome
PubMed: 38055420
DOI: 10.1590/1516-3180.2022.0401.R1.13032023