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Journal of Neurology, Neurosurgery, and... Jun 1990Five patients with neuroleptic malignant syndrome (NMS) are described. The syndrome developed earlier and took longer to resolve in patients with schizophrenic...
Five patients with neuroleptic malignant syndrome (NMS) are described. The syndrome developed earlier and took longer to resolve in patients with schizophrenic disorders. Deterioration in the level of consciousness presented earlier than rigidity and fever in all five patients and was thus considered a major criterion. A significant proportion of the patients showed abnormalities of gaze. In four of the five patients spontaneous recovery occurred without the need for specific drugs.
Topics: Adult; Affective Disorders, Psychotic; Antipsychotic Agents; Butyrophenones; Chlorpromazine; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Schizophrenia
PubMed: 1974283
DOI: 10.1136/jnnp.53.6.514 -
Neurotoxicity Research Jun 2021Synthetic cathinones appeared on the market in the 2000s as new psychoactive substances and gained significant prevalence among drug abusers. Cathinones produce...
Synthetic cathinones appeared on the market in the 2000s as new psychoactive substances and gained significant prevalence among drug abusers. Cathinones produce psychostimulant and empathogenic effects by enhancing dopaminergic, noradrenergic, and serotoninergic neurotransmission in the brain, and those which potently and selectively enhance dopaminergic transmission are considered to have higher abuse potential. The present study examines the behavioral effects related to psychostimulant properties, abuse potential, and addiction in DBA/2J mice of two cathinones with different profile of action on monoamine system, 4-chloromethcathinone (4-CMC), and 4-methoxy-pyrrolidinopentiophenone (4-MeO-PVP). 4-CMC and 4-MeO-PVP increase spontaneous locomotor activity after acute treatment and produce behavioral sensitization after 7-day intermittent treatment, which is a common feature of drugs of abuse. 4-MeO-PVP, but not 4-CMC, produces conditioned place preference after 4 days, indicating its rewarding properties. Finally, the ability of 4-CMC and 4-MeO-PVP to induce withdrawal symptoms after discontinuation from 14-day treatment was assessed using a battery of tests for behavioral markers of depression in mice: a tail suspension test, a forced swim test, measuring despair, and a sucrose preference test, measuring anhedonia. None of the three tests revealed increased depressive symptoms. Moreover, neither spontaneous locomotor activity nor motor performance on a rotarod was impaired after 14-day treatment with the tested compounds. These results indicate that 14-day treatment of mice with 4-CMC or 4-MeO-PVP does not induce significant withdrawal symptoms after cessation, nor significant impairment of dopaminergic circuitry resulting in motor impairment. The current study shows that 4-CMC and 4-MeO-PVP produce abuse-related behavioral changes in mice, which are more pronounced after more dopamine-selective 4-MeO-PVP.
Topics: Animals; Butyrophenones; Central Nervous System Stimulants; Conditioning, Psychological; Designer Drugs; Dopamine; Drug Administration Schedule; Locomotion; Male; Methylamines; Mice; Mice, Inbred DBA; Propiophenones; Pyrrolidines; Substance Withdrawal Syndrome; Time Factors
PubMed: 33428180
DOI: 10.1007/s12640-021-00329-x -
Molecular Cancer Therapeutics Oct 2020Enhancer of zester homolog 2 (EZH2), a histone lysine methyltransferase and the catalytic component of polycomb repressive complex 2, has been extensively investigated...
Enhancer of zester homolog 2 (EZH2), a histone lysine methyltransferase and the catalytic component of polycomb repressive complex 2, has been extensively investigated as a chromatin regulator and a transcriptional suppressor by methylating H3 at lysine 27 (H3K27). EZH2 is upregulated or mutated in most cancers, and its expression levels are negatively associated with clinical outcomes. However, the current developed small-molecule inhibitors targeting EZH2 enzymatic activities could not inhibit the growth and progression of solid tumors. Here, we discovered an antihistamine drug, ebastine, as a novel EZH2 inhibitor by targeting EZH2 transcription and subsequently downregulating EZH2 protein level and H3K27 trimethylation in multiple cancer cell lines at concentrations below 10 μmol/L. The inhibition of EZH2 by ebastine further impaired the progression, migration, and invasiveness of these cancer cells. Overexpression of wild-type and its mutant, (lacking methyltransferase activity), rescued the neoplastic properties of these cancer cells after ebastine treatment, suggesting that EZH2 targeted by ebastine is independent of its enzymatic function. Next-generation RNA-sequencing analysis also revealed that C4-2 cells treated with 8 μmol/L ebastine showed a gene profiling pattern similar to -knockdown C4-2 cells, which was distinctively different from cells treated with GSK126, an EZH2 enzyme inhibitor. In addition, ebastine treatment effectively reduced tumor growth and progression, and enhanced progression-free survival in triple-negative breast cancer and drug-resistant castration-resistant prostate cancer patient-derived xenograft mice. Our data demonstrated that ebastine is a novel, safe, and potent anticancer agent for patients with advanced cancer by targeting the oncoprotein EZH2.
Topics: Butyrophenones; Enhancer of Zeste Homolog 2 Protein; Female; Histamine H1 Antagonists; Humans; Male; Piperidines
PubMed: 32855270
DOI: 10.1158/1535-7163.MCT-20-0250 -
The Western Journal of Medicine Dec 1977
Topics: Adult; Chemical and Drug Induced Liver Injury; Cholestasis; Female; Haloperidol; Humans
PubMed: 595591
DOI: No ID Found -
British Medical Journal (Clinical... Jun 1983
Topics: Adult; Basal Ganglia Diseases; Chlorpromazine; Haloperidol; Humans; Male; Syndrome
PubMed: 6407647
DOI: 10.1136/bmj.286.6382.1938 -
Physiological Reports Apr 2021Local ischemic preconditioning (IPC) and remote ischemic conditioning (RIC) induced by brief periods of ischemia and reperfusion protect against ischemia-reperfusion...
BACKGROUND
Local ischemic preconditioning (IPC) and remote ischemic conditioning (RIC) induced by brief periods of ischemia and reperfusion protect against ischemia-reperfusion injury.
METHODS
We studied the sensitivity to IR-injury and the influence of strain, age, supplier, and anesthesia upon the efficacy of IPC and RIC in 7- and 16-weeks-old Sprague-Dawley and Wistar rats from three different suppliers. The influence of sedation with a hypnorm and midazolam mixture (rodent mixture) and pentobarbiturate was compared.
RESULTS
IPC attenuated infarct size in both 7-weeks-old Sprague-Dawley (48.4 ± 17.7% vs. 20.3 ± 6.9, p < 0.001) and 7-weeks-old Wistar (55.6 ± 10.9% vs. 26.8 ± 5.0%, p < 0.001) rats. Infarct size was larger in 16-weeks-old Sprague-Dawley rats, however, IPC still lowered infarct size (78.8 ± 9.2% vs. 58.3 ± 12.3%, p < 0.01). RIC reduced infarct sizes in 7-weeks-old Sprague-Dawley (75.3 ± 11.8% vs. 58.6 ± 8.9%, p < 0.05), but not in 7-weeks-old Wistar rats (31.7 ± 17.6% and 24.0 ± 12.6%, p = 0.2). In 16-weeks-old Sprague-Dawley rats, RIC did not induce protection (76.4 ± 5.5% and 73.2 ± 14.7%, p = 0.6). However, RIC induced protection in 16-weeks-old Wistar rats (45.2 ± 8.5% vs. 14.7 ± 10.8%, p < 0.001). RIC did not reduce infarct size in 7-weeks-old Sprague-Dawley rats from Charles River (62.0 ± 13.5% and 69.4 ± 10.4% p = 0.3) or 16-weeks-old Wistar rats from Janvier (50.7 ± 11.3 and 49.2 ± 16.2, p = 0.8). There was no difference between sedation with rodent mixture or pentobarbiturate.
CONCLUSION
The cardioprotective effect of IPC is consistent across rat strains independent of age, strain, and supplier. RIC seems to be less reproducible, but still yields protection across different rat strains. However, age, animal supplier, and anesthetics may modulate the sensitivity of IR-injury and the response to RIC.
Topics: Analgesia; Animals; Barbiturates; Butyrophenones; Drug Combinations; Fentanyl; Hypnotics and Sedatives; Ischemic Preconditioning; Isolated Heart Preparation; Male; Midazolam; Myocardial Reperfusion Injury; Rats; Rats, Sprague-Dawley; Rats, Wistar; Translational Research, Biomedical
PubMed: 33818005
DOI: 10.14814/phy2.14810 -
Journal of the South African Veterinary... Aug 2021Chemical immobilisation is essential for veterinarians to perform medical procedures in wild African ungulates. Potent opioids combined with neuroleptic drugs are most... (Comparative Study)
Comparative Study
Chemical immobilisation is essential for veterinarians to perform medical procedures in wild African ungulates. Potent opioids combined with neuroleptic drugs are most often used for this purpose. The present study aimed at comparing the quality of immobilisation and effects on physiological variables between a high (high etorphine-azaperone [HE]: 0.09 mg kg-1) and low etorphine dose (low etorphine-azaperone [LE]: 0.05 mg kg-1), both combined with azaperone (0.35 mg kg-1), in 12 adult female boma-acclimatised blesbok. It was hypothesised that a reduction in etorphine's dose in combination with azaperone would result in less cardiorespiratory impairment but likely worsen the quality of immobilisation. Both treatments resulted in rapid induction and recovery times. Overall inter-treatment differences occurred in pulse rate (HE and LE: 52 ± 15 and 44 ± 11 beats minute-1, p 0.0001), respiratory rate (HE and LE: 15 ± 4 and 17 ± 4 breaths minute-1, p 0.006), partial pressure of exhaled carbon dioxide (HE and LE: 62.0 ± 5.0 and 60.0 ± 5.6 millimetre of mercury [mmHg], p 0.028) and arterial carbon dioxide (HE and LE: 58.0 ± 4.5 and 55.0 ± 3.9 mmHg, p 0.002). Both HE and LE led to bradycardia, hypertension and marked hypoxia to a similar extent. Furthermore, quality of induction, immobilisation and recovery were similar in both treatments. The role of azaperone in the development of cardiorespiratory compromise and gas exchange impairment that occurred when these combinations were used is still unclear. Further studies are recommended to elucidate drug- and dose-specific physiological effects in immobilised antelope.
Topics: Animals; Antelopes; Azaperone; Drug Combinations; Etorphine; Female; Hypnotics and Sedatives; Immobilization; Monitoring, Physiologic
PubMed: 34476958
DOI: 10.4102/jsava.v92i0.2161 -
Anaesthesia Feb 2004
Topics: Adult; Analgesics, Opioid; Anesthesia, Local; Droperidol; Fentanyl; Humans; Peritonsillar Abscess
PubMed: 14725540
DOI: 10.1111/j.1365-2044.2003.03650.x -
Nature Jul 2017The cannabinoid receptor 1 (CB) is the principal target of the psychoactive constituent of marijuana, the partial agonist Δ-tetrahydrocannabinol (Δ-THC). Here we...
The cannabinoid receptor 1 (CB) is the principal target of the psychoactive constituent of marijuana, the partial agonist Δ-tetrahydrocannabinol (Δ-THC). Here we report two agonist-bound crystal structures of human CB in complex with a tetrahydrocannabinol (AM11542) and a hexahydrocannabinol (AM841) at 2.80 Å and 2.95 Å resolution, respectively. The two CB-agonist complexes reveal important conformational changes in the overall structure, relative to the antagonist-bound state, including a 53% reduction in the volume of the ligand-binding pocket and an increase in the surface area of the G-protein-binding region. In addition, a 'twin toggle switch' of Phe200 and Trp356 (superscripts denote Ballesteros-Weinstein numbering) is experimentally observed and appears to be essential for receptor activation. The structures reveal important insights into the activation mechanism of CB and provide a molecular basis for predicting the binding modes of Δ-THC, and endogenous and synthetic cannabinoids. The plasticity of the binding pocket of CB seems to be a common feature among certain class A G-protein-coupled receptors. These findings should inspire the design of chemically diverse ligands with distinct pharmacological properties.
Topics: Binding Sites; Cannabinoid Receptor Agonists; Crystallography, X-Ray; Dronabinol; Droperidol; Heterotrimeric GTP-Binding Proteins; Humans; Ligands; Molecular Docking Simulation; Protein Binding; Protein Conformation; Receptor, Cannabinoid, CB1
PubMed: 28678776
DOI: 10.1038/nature23272 -
European Review For Medical and... Feb 2021Delirium, a common behavioral manifestation of acute brain dysfunction in Intensive Care Unit (ICU), is a significant contributor to mortality and worse long-term... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Delirium, a common behavioral manifestation of acute brain dysfunction in Intensive Care Unit (ICU), is a significant contributor to mortality and worse long-term outcome. Antipsychotics, especially haloperidol, are commonly administered for the treatment and prevention of delirium in critically ill patients while the evidence for the safety and efficacy of these drugs is still lacking. Therefore, we conducted a systematic review of the benefits of haloperidol for the prevention of delirium in ICU patients.
MATERIALS AND METHODS
We made a systematic review and meta-analysis.
RESULTS
Eight RCTs with 2806 patients were included. The prophylactic use of haloperidol did not reduce the delirium incidence (RR: 0.90, 95% CI: 0.69-1.71), the duration of delirium (MD: -0.33, 95% CI: -1.25-0.588) and the delirium/coma free days (MD: 0.08, 95% CI: -0.06-0.23). We did not find an increase of extrapyramidal effects (RR: 1.86, 95% CI: 0.30-11.39), QTc prolongation (RR: 1.11, 95% CI: 0.79-1.55) and arrhythmias (RR: 1.26, 95% CI: 0.72-2.19). The use of haloperidol did not increase the ICU (MD: 0.77, 95% CI: -0.28-1.83) and hospital length of stay (MD: -0.57, 95% CI: -1.32-0.18). Haloperidol did not increase the sedation level (RR: 1.88, 95% CI: 0.76-4.63) and mortality (RR: 0.97, 95% CI: 0.83-1.18).
CONCLUSIONS
Haloperidol did not reduce the delirium incidence, the delirium duration, the delirium/coma free-days and did not increase the incidence of extrapyramidal effects, arrhythmias, the ICU and hospital length of stays and sedation.
Topics: Antipsychotic Agents; Delirium; Haloperidol; Humans; Intensive Care Units
PubMed: 33629327
DOI: 10.26355/eurrev_202102_24868