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1.
J Clin Psychiatry ; 85(3)2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39196883

RESUMEN

Drugs have actions that may be classified as therapeutic effects and side effects; side effects are actions that do not contribute to therapeutic benefit. Some side effects are neutral; others, experienced as undesirable or unpleasant, are recorded as adverse effects. Some drug actions are therapeutic for some disorders and adverse for others; or therapeutic during acute illness and adverse during maintenance treatment. As an example, anticholinergic action may be adverse when a tricyclic antidepressant is used to treat depression but therapeutic when the drug is used to treat irritable bowel syndrome with diarrhea. In clinical practice, side or adverse effects of a drug may be leveraged to manage troublesome symptoms. As an example, the sedative effect of a low dose of trazodone may be useful for some patients with insomnia. With this background, studies have examined whether the increase in appetite and weight associated with olanzapine and mirtazapine may be effective against anorexia and cachexia associated with cancer and cancer chemotherapy. The subject is important because cachexia may be present in 30%-50% of patients with cancer (with higher prevalence in patients with more advanced cancer) and because the presence of cachexia is associated with a higher risk of disease progression and mortality. Many randomized controlled trials (RCTs) have examined pharmacologic interventions such as progestins, corticosteroids, anamorelin, and medical cannabis for cancer related cachexia; most results have been disappointing. A recent RCT found that olanzapine (2.5 mg/d for 12 weeks) improved appetite, weight, other nutritional parameters, and quality of life in patients with locally advanced or metastatic cancer treated with chemotherapy. Another RCT, however, found that mirtazapine (30 mg/d for 8 weeks) brought no nutritional or anthropometric gain in patients with cancer and anorexia. It is concluded that olanzapine but not mirtazapine merits further investigation in patients with cancer who have anorexia and cachexia.


Asunto(s)
Anorexia , Benzodiazepinas , Caquexia , Mianserina , Mirtazapina , Neoplasias , Olanzapina , Humanos , Mirtazapina/uso terapéutico , Mirtazapina/efectos adversos , Olanzapina/uso terapéutico , Olanzapina/efectos adversos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Anorexia/inducido químicamente , Anorexia/tratamiento farmacológico , Mianserina/análogos & derivados , Mianserina/efectos adversos , Mianserina/uso terapéutico , Benzodiazepinas/efectos adversos , Benzodiazepinas/uso terapéutico , Benzodiazepinas/farmacología , Caquexia/tratamiento farmacológico , Caquexia/etiología , Caquexia/inducido químicamente , Antipsicóticos/efectos adversos , Antipsicóticos/uso terapéutico , Antidepresivos Tricíclicos/efectos adversos , Antidepresivos Tricíclicos/uso terapéutico
2.
J Vet Cardiol ; 53: 72-76, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38735230

RESUMEN

A nine-year-old spayed female domestic shorthair cat with a previous diagnosis of hypertrophic cardiomyopathy and treated for one month with atenolol (6.25 mg q 12 h) was referred for respiratory distress and anorexia. The cat was diagnosed with pulmonary oedema secondary to obstructive hypertrophic cardiomyopathy. After stabilisation, she was discharged with furosemide (1 mg/kg q 12 h), clopidogrel (18.75 mg q 24 h), atenolol (6.25 mg q 12 h), and mirtazapine (2 mg/cat q 24 h) to increase appetite. At recheck, the cat was lethargic and presented with severe bradycardia with a junctional escape rhythm and ventriculoatrial conduction. The mirtazapine was discontinued due to its possible side-effects on cardiac rhythm. After three days, the atenolol was halved because the bradyarrhythmia was still present. After 10 days, the rhythm returned to sinus; atenolol was reintroduced twice daily with no further side-effects. The absence of a sinus rhythm with a junctional escape rhythm and P' retroconduction is compatible with a third-degree sinus block or a sinus standstill; the differentiation of these rhythm disturbances is impossible, based on the surface electrocardiogram (ECG). The sinus rhythm was restored after mirtazapine was withdrawn. However, it is not possible to rule out the role of the atenolol or the combined effect of the two drugs. The cat was affected by hypertrophic cardiomyopathy, and the role of myocardial remodelling cannot be excluded. This is the first time that a bradyarrhythmia consequent to the treatment with atenolol and mirtazapine was described in a cat.


Asunto(s)
Atenolol , Bradicardia , Cardiomiopatía Hipertrófica , Enfermedades de los Gatos , Mirtazapina , Femenino , Mirtazapina/uso terapéutico , Animales , Atenolol/uso terapéutico , Atenolol/efectos adversos , Gatos , Enfermedades de los Gatos/tratamiento farmacológico , Cardiomiopatía Hipertrófica/veterinaria , Cardiomiopatía Hipertrófica/tratamiento farmacológico , Bradicardia/veterinaria , Bradicardia/inducido químicamente , Bradicardia/tratamiento farmacológico , Mianserina/análogos & derivados , Mianserina/uso terapéutico , Mianserina/efectos adversos , Antagonistas de Receptores Adrenérgicos beta 1/uso terapéutico , Antagonistas de Receptores Adrenérgicos beta 1/efectos adversos
3.
Artículo en Ruso | MEDLINE | ID: mdl-38676680

RESUMEN

Epidemiological studies indicate that about 35% of the world's population periodically suffer from insomnia. Many authors in their studies note sleep disturbances in the clinic of both somatic and mental disorders, often considering sleep disturbances as one of the predictors of these diseases. In psychiatric practice, sleep disorders are most often described in the clinic of depression, which is determined by the general pathophysiological mechanisms of their development due to disruption of the activity of the main neurotransmitter systems of the brain. The results of clinical studies show that the drug of choice in the treatment of sleep disorders in the depression clinic is the antidepressant Mirtazapine, which has a unique profile of pharmacological activity. According to international recommendations, Mirtazapine is a first-line drug in the treatment of anxiety and depressive disorders with sleep disorders and sexual dysfunction caused by taking other antidepressants.


Asunto(s)
Mirtazapina , Trastornos del Sueño-Vigilia , Humanos , Mirtazapina/uso terapéutico , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Mianserina/análogos & derivados , Mianserina/uso terapéutico , Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Trastorno Depresivo/tratamiento farmacológico
4.
Sci Adv ; 10(16): eadk4855, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38630816

RESUMEN

Serotonin [5-hydroxytryptamine (5-HT)] acts via 13 different receptors in humans. Of these receptor subtypes, all but 5-HT1eR have confirmed roles in native tissue and are validated drug targets. Despite 5-HT1eR's therapeutic potential and plausible druggability, the mechanisms of its activation remain elusive. To illuminate 5-HT1eR's pharmacology in relation to the highly homologous 5-HT1FR, we screened a library of aminergic receptor ligands at both receptors and observe 5-HT1eR/5-HT1FR agonism by multicyclic drugs described as pan-antagonists at 5-HT receptors. Potent agonism by tetracyclic antidepressants mianserin, setiptiline, and mirtazapine suggests a mechanism for their clinically observed antimigraine properties. Using cryo-EM and mutagenesis studies, we uncover and characterize unique agonist-like binding poses of mianserin and setiptiline at 5-HT1eR distinct from similar drug scaffolds in inactive-state 5-HTR structures. Together with computational studies, our data suggest that these binding poses alongside receptor-specific allosteric coupling in 5-HT1eR and 5-HT1FR contribute to the agonist activity of these antidepressants.


Asunto(s)
Mianserina , Serotonina , Humanos , Mianserina/farmacología , Antidepresivos , Receptores de Serotonina/metabolismo , Transducción de Señal
5.
JAMA Netw Open ; 7(3): e241527, 2024 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-38451521

RESUMEN

Importance: Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA. Objective: To compare the efficacy associated with AIA treatments. Data Sources: Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023. Study Selection: Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded. Data Extraction and Synthesis: Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. Main Outcomes and Measures: The primary outcome was the severity of akathisia measured by a validated scale at the last available end point. Results: Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found. Conclusions and Relevance: In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.


Asunto(s)
Acatisia Inducida por Medicamentos , Antipsicóticos , Humanos , Antipsicóticos/efectos adversos , Biperideno , Ciproheptadina , Galopamilo , Mianserina , Mirtazapina/uso terapéutico , Metaanálisis en Red , Propranolol , Ensayos Clínicos Controlados Aleatorios como Asunto , Trazodona , Vitamina B 6 , Acatisia Inducida por Medicamentos/tratamiento farmacológico
6.
Drug Deliv Transl Res ; 14(9): 2539-2557, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38376620

RESUMEN

Mirtazapine (MZPc) is an antidepressant drug which is approved by the FDA. It has low bioavailability, which is only 50%, in spite of its rapid absorption when orally administered owing to high first-pass metabolism. This study was oriented towards delivering intranasal (IN) mirtazapine by a direct route to the brain by means of preparing lipid nanocapsules (LNCs) as a targeted drug delivery system. MZP-LNCs were constructed by solvent-free phase inversion temperature technique applying D-Optimal mixture design to study the impact of 3 formulation variables on the characterization of the formulated nanocapsules. Independent variables were percentage of Labrafac oil, percentage of Solutol and percentage of water. Dependent variables were particle size, polydispersity index (PDI), Zeta potential and solubilization capacity. Nanocapsules of the optimized formula loaded with MZP were of spherical shape as confirmed by transmission electron microscopy with particle diameter of 20.59 nm, zeta potential of - 5.71, PDI of 0.223 and solubilization capacity of 7.21 mg/g. The in vivo pharmacokinetic behavior of intranasal MZP-LNCs in brain and blood was correlated to MZP solution after intravenous (IV) and intranasal administration in mice. In vivo biodistribution of the drug in mice was assessed by a radiolabeling technique using radioiodinated mirtazapine (131I-MZP). Results showed that intranasal MZP-LNCs were able to deliver higher amount of MZP to the brain with less drug levels in blood when compared to the MZP solution after IV and IN administration. Moreover, the percentage of drug targeting efficiency (%DTE) of the optimized MZP-LNCs was 332.2 which indicated more effective brain targeting by the intranasal route. It also had a direct transport percentage (%DTP) of 90.68 that revealed a paramount contribution of the nose to brain pathway in the drug delivery to the brain.


Asunto(s)
Administración Intranasal , Encéfalo , Lípidos , Mirtazapina , Nanocápsulas , Animales , Mirtazapina/farmacocinética , Mirtazapina/administración & dosificación , Mirtazapina/química , Encéfalo/metabolismo , Distribución Tisular , Nanocápsulas/química , Lípidos/química , Lípidos/farmacocinética , Lípidos/administración & dosificación , Masculino , Ratones , Sistemas de Liberación de Medicamentos , Tamaño de la Partícula , Radioisótopos de Yodo/farmacocinética , Radioisótopos de Yodo/administración & dosificación , Mucosa Nasal/metabolismo , Mianserina/farmacocinética , Mianserina/administración & dosificación , Mianserina/química , Mianserina/análogos & derivados , Mianserina/sangre
7.
Jpn J Clin Oncol ; 54(5): 530-536, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38323684

RESUMEN

OBJECTIVE: Cancer-related anorexia-cachexia comprises one of the most common syndromes of advanced cancer patients. The management of cancer-related anorexia-cachexia is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of cancer-related anorexia-cachexia. This study is considered to find out whether there is any role of mirtazapine in the improvement of anorexia in cancer patients. METHODS: A total of 80 cancer-anorexia patients were enrolled. Patients in the trial arm received the standard chemotherapy medication plus one tablet of mirtazapine 15 mg daily at night orally for 8 weeks starting from the day of an initial assessment. The control arm received the standard chemotherapy medication plus one tablet of megestrol acetate 160 mg daily orally for 8 weeks starting from the day of an initial assessment. Each patient was assessed by validated versions of Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale v 4 questionnaires. RESULTS: After 4 and 8 weeks each patient was evaluated again using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale tool. The quality of life of each patient was assessed by European Organization for Research and Treatment QLQ-C30 v 3.0. After 4 to 8 weeks of treatment, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Sub Scale score in cancer anorexia patients in the mirtazapine improved anorexia significantly. However, the improvement after 4 to 8 weeks was not statistically significant when it was compared with the megestrol acetate (P > 0.05). CONCLUSIONS: Therefore, the findings of this study reveal that mirtazapine might be a potential alternative to megestrol acetate, as it has shown potential efficacy as like as megestrol acetate.


Asunto(s)
Anorexia , Caquexia , Acetato de Megestrol , Mirtazapina , Neoplasias , Calidad de Vida , Humanos , Mirtazapina/uso terapéutico , Mirtazapina/administración & dosificación , Anorexia/tratamiento farmacológico , Anorexia/etiología , Acetato de Megestrol/uso terapéutico , Acetato de Megestrol/administración & dosificación , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Femenino , Caquexia/tratamiento farmacológico , Caquexia/etiología , Método Doble Ciego , Anciano , Adulto , Mianserina/análogos & derivados , Mianserina/uso terapéutico , Mianserina/administración & dosificación , Estimulantes del Apetito/uso terapéutico , Estimulantes del Apetito/administración & dosificación
8.
Eur J Pharmacol ; 959: 176064, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37758013

RESUMEN

We previously reported that in different cell types antidepressant drugs activate lysophosphatidic acid (LPA) LPA1 receptor to induce proliferative and prosurvival responses. Here, we further characterize this unique action of antidepressants by examining their effects on two additional LPA receptor family members, LPA2 and LPA3. Human LPA1-3 receptors were stably expressed in HEK-293 cells (HEK-LPA1, -LPA2 and -LPA3 cells) and their functional activity was determined by Western blot and immunofluorescence. LPA effectively stimulated the phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in HEK-LPA1, -LPA2, and -LPA3 cells. The tricyclic antidepressants amitriptyline, clomipramine, imipramine and desipramine increased phospho-ERK1/2 levels in HEK-LPA1 and -LPA3 cells but were relatively poor agonists in LPA2-expressing cells. The tetracyclic antidepressants mianserin and mirtazapine were active at all three LPA receptors. When combined with LPA, both amitriptyline and mianserin potentiated Gi/o-mediated phosphorylation of ERK1/2 induced by LPA in HEK-LPA1, -LPA2 and -LPA3 cells, CHO-K1 fibroblasts and HT22 hippocampal neuroblasts. This potentiation was associated with enhanced phosphorylation of CREB and S6 ribosomal protein, two molecular targets of activated ERK1/2. The antidepressants also potentiated LPA-induced Gq/11-mediated phosphorylation of AMP-activated protein kinase in HEK-LPA1 and -LPA3 cells. Conversely, amitriptyline and mianserin were found to inhibit LPA-induced Rho activation in HEK-LPA1 and LPA2 cells. These results indicate that tricyclic and tetracyclic antidepressants can act on LPA1, LPA2 and LPA3 receptor subtypes and exert differential effects on LPA signalling through these receptors.


Asunto(s)
Amitriptilina , Mianserina , Humanos , Mianserina/farmacología , Amitriptilina/farmacología , Células HEK293 , Antidepresivos/farmacología , Lisofosfolípidos/farmacología , Lisofosfolípidos/metabolismo , Receptores del Ácido Lisofosfatídico/metabolismo
9.
Int J Mol Sci ; 24(13)2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37446323

RESUMEN

About 30% of major depression disorder patients fail to achieve remission, hence being diagnosed with treatment-resistant major depression (TRD). Opium had been largely used effectively to treat depression for centuries, but when other medications were introduced, its use was discounted due to addiction and other hazards. In a series of previous studies, we evaluated the antinociceptive effects of eight antidepressant medications and their interaction with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of mianserin, mirtazapine, trazodone, venlafaxine, reboxetine, moclobemide, fluoxetine, or fluvoxamine to determine the effect of each drug in eliciting antinociception. When naloxone inhibited the antinociceptive effect, we further examined the effect of the specific opioid antagonists of each antidepressant drug. Mianserin and mirtazapine (separately) induced dose-dependent antinociception, each one yielding a biphasic dose-response curve, and they were antagonized by naloxone. Trazodone and venlafaxine (separately) induced a dose-dependent antinociceptive effect, antagonized by naloxone. Reboxetine induced a weak antinociceptive effect with no significant opioid involvement, while moclobemide, fluoxetine, and fluvoxamine had no opioid-involved antinociceptive effects. Controlled clinical studies are needed to establish the efficacy of the augmentation of opiate antidepressants in persons with treatment-resistant depression and the optimal dosage of drugs prescribed.


Asunto(s)
Analgésicos Opioides , Trazodona , Animales , Ratones , Analgésicos Opioides/farmacología , Analgésicos Opioides/uso terapéutico , Mianserina/farmacología , Mianserina/uso terapéutico , Clorhidrato de Venlafaxina/farmacología , Clorhidrato de Venlafaxina/uso terapéutico , Fluvoxamina , Mirtazapina/farmacología , Mirtazapina/uso terapéutico , Fluoxetina , Reboxetina , Moclobemida , Depresión , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Naloxona/farmacología , Naloxona/uso terapéutico , Relación Dosis-Respuesta a Droga
13.
Anticancer Res ; 43(3): 1201-1206, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36854516

RESUMEN

BACKGROUND/AIM: An epidemiological investigation indicated that tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) were associated with a lower risk of hepatocellular carcinoma (HCC). Another previous study showed that seven antidepressants inhibited glucocorticoid receptor (GR)-mediated gene transcription, a pathway that is linked to various diseases, including cancer. It is known that the expression levels of GR in cancerous tissues are higher than those in noncancerous tissues in patients with HCC. Notably, among the seven antidepressants, amitriptyline (TCA), desipramine (TCA), and fluoxetine (SSRI) were found to induce apoptosis in HCC cells. Given this, we investigated whether four other GR-specific antidepressants, including mianserin (atypical antidepressant), tianeptine (atypical antidepressant), imipramine (TCA), and moclobemide (monoamine oxidase inhibitor, MAOI) affect the cell viability of HCC. MATERIALS AND METHODS: Cell proliferation and IC50 curves were determined by MTT assays. RESULTS: Imipramine and mianserin significantly inhibited HCC cell viability, whereas moclobemide and tianeptine did not. IC50 showed that the same dose of imipramine or mianserin led to significant inhibitory effects on HCC cells whereas there were only slight effects on normal human hepatocytes (HH). CONCLUSION: According to previous and present findings, TCAs, SSRIs and mianserin may have anti-tumor activity in HCC. However, the appropriate dose, frequency, and route of the administration still need to be determined in future preclinical and clinical studies.


Asunto(s)
Antidepresivos de Segunda Generación , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Mianserina , Imipramina/farmacología , Moclobemida , Inhibidores Selectivos de la Recaptación de Serotonina , Neoplasias Hepáticas/tratamiento farmacológico , Antidepresivos/farmacología
14.
J Psychiatr Pract ; 29(1): 58-70, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36649554

RESUMEN

OBJECTIVE: Antidepressant-induced pancreatitis is a rare, albeit serious, adverse effect, with a frequency of occurrence that is not equally distributed among antidepressant drugs. The goal of this study was to investigate the association and causal relationship between mirtazapine treatment of patients with depression and pancreatitis. METHODS: The study was designed as a systematic review of the literature, accompanied by the description of a new case of mirtazapine-associated acute pancreatitis. RESULTS: Nine cases of mirtazapine-associated pancreatitis have been reported, involving 7 female patients and 2 male patients with a mean age of 46.4 years (range: 26 to 83 y of age). All of the patients were hospitalized, with an average length of stay of 16.2 days (range: 3 to 34 d). In 6 cases, "de-challenge" followed by improvement was reported. The patients for whom the outcome was reported (7 of 9) recovered completely. CONCLUSION: Although a rare adverse effect, mirtazapine-induced pancreatitis should be considered when patients taking mirtazapine report abdominal discomfort.


Asunto(s)
Depresión , Pancreatitis , Humanos , Masculino , Femenino , Persona de Mediana Edad , Mirtazapina/uso terapéutico , Enfermedad Aguda , Depresión/tratamiento farmacológico , Pancreatitis/inducido químicamente , Pancreatitis/tratamiento farmacológico , Antidepresivos/efectos adversos , Mianserina/efectos adversos , Antidepresivos Tricíclicos/efectos adversos
15.
Soc Psychiatry Psychiatr Epidemiol ; 58(10): 1493-1502, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36562827

RESUMEN

AIM: To describe trends in and characteristics of sedative drug use from 2000 through 2019 in relation to the introduction of central regulations and new drugs. METHODS: In this descriptive study, we used individual prescription data on the entire Danish population from the Danish National Prescription Registry to calculate yearly incidence and prevalence of use of benzodiazepines, benzodiazepine-related drugs (Z-drugs), melatonin, olanzapine, low-dose quetiapine, mianserin/mirtazapine, pregabalin, and promethazine from 2000 through 2019. From the Danish National Patient Registry, we obtained data on drug users' psychiatric and somatic comorbidity. RESULTS: The use of benzodiazepines and Z-drugs declined gradually from 2000 through 2019, whereas the newer alternatives, melatonin, low-dose quetiapine, pregabalin and promethazine, increased in use, while the use of olanzapine and mianserin/mirtazapine was relatively stable. This development was seen in both men and women and across all age groups except for hypnotic benzodiazepines which showed a steep increase in the oldest age group from 2010. For all sedative drugs depression, anxiety, alcohol and misuse disorder, pain and cancer were the most prevalent comorbidities. During our study period, the number of individuals without any of the selected diagnoses increased. CONCLUSION: In Denmark different central regulations have influenced prescription practice toward more restrictive use of Z-drugs and benzodiazepines, except for hypnotic benzodiazepine prescriptions increased after the introduction of special palliative care. An increase in use of newer sedative drugs, however, indicates that the regulations do not remove the need for sedative drugs in the population.


Asunto(s)
Melatonina , Trastornos Relacionados con Sustancias , Masculino , Humanos , Femenino , Hipnóticos y Sedantes/uso terapéutico , Pregabalina , Olanzapina , Fumarato de Quetiapina , Mirtazapina , Mianserina , Prometazina , Prescripciones de Medicamentos , Benzodiazepinas/uso terapéutico , Trastornos Relacionados con Sustancias/epidemiología , Utilización de Medicamentos , Dinamarca/epidemiología
16.
Pestic Biochem Physiol ; 189: 105290, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36549826

RESUMEN

In the last decades, the entomotoxicity of JBU and its derived peptides became an object of study, due mainly to the ubiquitous interaction of these compounds with different species of insects and their potential as natural insecticides. In this work, we investigated the neurotoxic effects of JBU in Nauphoeta cinerea cockroaches by dissecting pharmacologically the monoaminergic pathways involved. Selective pharmacological modulators for monoaminergic pathways in in vivo and ex vivo experimental models were employed. Thus, the analysis of N. cinerea neurolocomotory behavior demonstrated that JBU (1.5 and 3 µg/g) induces a significant decrease in the exploratory activity. In these assays, pretreatment of animals with phentolamine, SCH23390 or reserpine, interfered significantly with the response of JBU. Using in vivo abductor metathoracic preparations JBU (1.5 µg/g) induced progressive neuromuscular blockade, in 120 min recordings. In this set of experiments, the previous treatment of the animals with phentolamine, SCH23390 or reserpine, completely inhibited JBU-induced neuromuscular blockade. The recordings of spontaneous compound neural action potentials in N. cinerea legs showed that JBU, only in the smallest dose, significantly decreased the number of potentials in 60 min recordings. When the animals were pretreated with phentolamine, SCH23390, or reserpine, but not with mianserin, there was a significant prevention of the JBU-inhibitory responses on the action potentials firing. Meanwhile, the treatment of the animals with mianserin did not affect JBU's inhibitory activity. The data presented in this work strongly suggest that the neurotoxic response of JBU in N. cinerea involves a cross talking between OCTOPAMIN-ergic and DOPAMIN-ergic nerve systems, but not the SEROTONIN-ergic neurotransmission. Further molecular biology studies with expression of insect receptors associated with voltage clamp techniques will help to discriminate the selectivity of JBU over the monoaminergic transmission.


Asunto(s)
Cucarachas , Ureasa , Animales , Ureasa/farmacología , Fentolamina/farmacología , Mianserina/farmacología , Reserpina/farmacología
17.
Neurotoxicol Teratol ; 96: 107148, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36539103

RESUMEN

There is a lack of data on the effects of chronic exposure to common drugs and stimulants on the developing nervous system. Freshwater planarians have emerged as a useful invertebrate model amenable to high-throughput behavioral phenotyping to assay chemical safety in adult and developing brains. Here, we leverage the unique strength of the system to test in parallel for effects on the adult and developing nervous system, by screening ten common drugs and stimulants (forskolin, clenbuterol, LRE-1, MDL-12,330A, adenosine, caffeine, histamine, mianserin, fluoxetine and sertraline) using the asexual freshwater planarian Dugesia japonica. The compounds were tested up to 100 µM nominal concentration for their effects on planarian morphology and behavior. Quantitative phenotypic assessments were performed on days 7 and 12 of exposure using an automated screening platform. The antidepressants sertraline and fluoxetine were the most potent to induce lethality, with significant lethality observed at 10 µM. All ten compounds caused sublethal morphological and/or behavioral effects, with the most effects, in terms of potency and breadth of endpoints affected, seen with mianserin and fluoxetine. Four of the compounds (forskolin, clenbuterol, mianserin, and fluoxetine) were developmentally selective, causing effects at lower concentrations in regenerating planarians. Of these, fluoxetine showed the greatest differences between the two developmental stages, inducing many behavioral endpoints in regenerating planarians but only a few in adult planarians. While some of these behavioral effects may be due to neuroefficacy, these results substantiate the need for better evaluation of the safety of these common drugs on the developing nervous system.


Asunto(s)
Clenbuterol , Planarias , Animales , Fluoxetina/toxicidad , Mianserina/farmacología , Clenbuterol/farmacología , Colforsina/farmacología , Sertralina
19.
J Clin Psychopharmacol ; 42(6): 560-564, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36306393

RESUMEN

BACKGROUND: Although antipsychotics are commonly used for delirium, their adverse effects are a serious concern in light of extrapyramidal symptoms and cardiovascular disturbances. In clinical practice, sedative antidepressants are frequently used as an alternative treatment for delirium; however, there is scarce evidence. Thus, we conducted a retrospective chart review to examine the use and effectiveness of trazodone and mianserin for delirium. METHODS: Patients who were admitted to a university hospital during 4 years and received either trazodone or mianserin on a regular schedule as monotherapy for the treatment of delirium were included. The rates of and times to the improvement of delirium were compared. RESULTS: Among 3971 patients who developed delirium, 379 (9.5%) and 341 (8.6%) patients received trazodone and mianserin on a regular schedule; 52 and 46 patients met the eligibility criteria (ie, monotherapy) for trazodone and mianserin, respectively. The percentages of patients 65 years or older were 86.5% (n = 45) for trazodone and 89.1% (n = 41) for mianserin. The rates of the improvement of delirium were 63.5% for trazodone and 50.0% for mianserin. Times to the improvement of delirium were 5.3 days (95% confidence interval, 3.2-7.4 days) for trazodone and 9.3 days (95% confidence interval, 5.3-13.3 days) for mianserin. There were no significant differences in the primary outcomes between the 2 groups ( P = 0.17 and P = 0.13, respectively). CONCLUSION: Considering potentially serious, sometimes lethal, adverse effects of antipsychotics, sedative antidepressants such as trazodone and mianserin may be a treatment option for delirium, especially in the elderly.


Asunto(s)
Antipsicóticos , Delirio , Trazodona , Humanos , Anciano , Trazodona/efectos adversos , Mianserina/efectos adversos , Estudios Retrospectivos , Antidepresivos/uso terapéutico , Antipsicóticos/efectos adversos , Delirio/tratamiento farmacológico , Delirio/inducido químicamente , Hipnóticos y Sedantes
20.
J Chromatogr A ; 1680: 463430, 2022 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-36030567

RESUMEN

In this paper, the potential of micellar solutions of the anionic surfactant sodium dodecyl sulfate (SDS) as eluents in dispersive micro-solid phase extraction (D-µSPE) using polydopamine-coated magnetite nanoparticles (Fe3O4@PDA NPs) for the extraction and preconcentration of seven basic drugs (bupropion, citalopram, fluoxetine, mianserin, nomifensine, trimipramine, and viloxazine) is explored for the first time (to the best to our knowledge) and compared with conventional hydro-organic eluents. The impact of the sample solution pH, Fe3O4@PDA NPs and PDA coating amounts and extraction time on the extraction efficiency (EE), as well as the composition of the eluent on the overall efficiency (OE) are studied. Under the selected experimental conditions (50 mg of Fe3O4@PDA NPs, 100 µL of 1 M NH3, 5 min of extraction time and 0.15 M SDS at pH 2.6 as eluent), EE and OE values were higher than 90% for all compounds and for the most hydrophobic compounds (trimipramine, fluoxetine and mianserin), respectively. The results shown in this paper demonstrate the suitability of Fe3O4@PDA NPs as a sorbent for the extraction of antidepressants as well as the advantages of using SDS micellar solutions over classic hydro-organic eluents containing methanol, acetonitrile or tetrahydrofuran. Finally, the stability and reusability of the Fe3O4@PDA NPs is proven.


Asunto(s)
Nanopartículas de Magnetita , Antidepresivos , Cromatografía Líquida de Alta Presión/métodos , Fluoxetina , Indoles , Fenómenos Magnéticos , Nanopartículas de Magnetita/química , Mianserina , Micelas , Polímeros , Dodecil Sulfato de Sodio/química , Extracción en Fase Sólida/métodos , Trimipramina
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