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1.
Tijdschr Psychiatr ; 61(7): 498-503, 2019.
Artigo em Holandês | MEDLINE | ID: mdl-31372971

RESUMO

Three patients suffering from a treatment-resistant depression were being treated with a monoamine oxidase (mao-)inhibitor and received lithium augmentation to achieve better recovery. One patient showed significant improvement of depressive symptoms within 24 hours, one patient showed very little respons and one patient did not respond at all. Literature research led to other casereports, where adding lithium to mao-inhibitors had also been effective. The growing amount of arguments of a positive effect of lithium augmentation to mao-inhibitors asks for more research to collect more evidence and a better understanding of this new, potentially effective treatment.


Assuntos
Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Lítio/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Antidepressivos/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
3.
Drugs Aging ; 36(9): 807-821, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31161581

RESUMO

Levodopa is the mainstay of treatment in Parkinson's disease (PD). As the disease progresses, variations in plasma levodopa levels lead to motor fluctuations. The common reasons behind variations in the plasma levels include delayed gastric emptying, small intestinal bacterial overgrowth, protein interaction with levodopa absorption, and limited oral bioavailability of levodopa. Efforts to find newer delivery systems for older drugs to avoid the problems associated with oral delivery of medications are continuing. This review aims to provide up-to-date information about the newer delivery options for drugs used for PD and provides a summary of infusion therapy with apomorphine, modifications to other dopamine agonists, various oral formulations of carbidopa/levodopa, inhaled levodopa, intrajejunal infusion of levodopa, and sublingual apomorphine. The advantages, dose, and adverse effects of each treatment modality are reviewed. We also discuss several drugs under investigation, such as the subcutaneous carbidopa/levodopa infusion and subcutaneous rotigotine.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Humanos , Levodopa/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico
4.
Ideggyogy Sz ; 72(5-6): 187-193, 2019 May 30.
Artigo em Húngaro | MEDLINE | ID: mdl-31241263

RESUMO

Background and purpose: There is relatively few data regarding the usage of dopaminagonists for the treatment of Parkinson's disease; furthermore, there are no publications regarding Central- and Eastern-European countries. The aim of the study was to evaluate the use of dopamine agonists as a therapeutic option amongst Parkinson's disease patients admitted to the Neurological Clinics of Tîrgu Mures during the last 15 years. Methods: In our study we investigated the data of all Parkinson's patients treated at our clinics between the 1st of January 2003 and the 31st of December 2017. We analyzed the particularities of dopamine agonists' usage based on the therapeutic recommendations from the final report of these patients. Regarding time since the diagnosis, we divided the patients in two groups: less than or equal to 5 years and more than 5 years. Results: During the studied period a total of 2379 patients with Parkinson's disease were treated at the Clinics. From the 1237 patients with disease duration under 5 years 665 received dopamine agonists: 120 as monotherapy, 83 together with monoamine oxidase inhibitors and in 234 cases associated with levodopa. The remaining 228 patients were treated with a triple combination of levodopa, dopamine agonists and monoamine oxidase inhibitors. In patients suffering from Parkinson's disease for more than 5 years, in 364 cases out of 653 a dopamine agonist was part of the therapy. Conclusion: The usage of dopamine agonists was similar to the data presented in other studies. We consider that clinicians treating the disease should, with the necessary prudence, use the available and recommended dopamine agonist with the utmost courage to their maximum therapeutic potential.


Assuntos
Antiparkinsonianos/uso terapêutico , Agonistas de Dopamina/uso terapêutico , Levodopa/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Estudos Transversais , Humanos , Resultado do Tratamento
5.
Expert Opin Pharmacother ; 20(11): 1351-1363, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31120798

RESUMO

INTRODUCTION: Depression is a common non-motor symptom in Parkinson disease (PD), occurring in approximately 20% of patients with PD. While depression can occur anytime in the disease process, it predates PD diagnosis in about 30% of patients. Between 20% and 60% of depressed patients with PD are either without recognition or treatment of their depression. AREAS COVERED: The pathophysiology of depression in PD is unclear. There are several structural changes seen in depressed patients with PD that are also seen in patients with depression. In addition, the neurotransmitters dopamine, serotonin, and norepinephrine are all depleted in PD. This article covers the pharmacological treatment of depression in PD; this involves standard antidepressant treatment such as selective serotonin reuptake inhibitors, tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors. As with depression not associated with PD, most treatment is partially successful. Non-pharmacological approaches are also touched upon. EXPERT OPINION: Most antidepressant therapy shows partial efficacy in patients with PD. However, there is a need for better study design as well as more comparative studies for the treatment of depression in PD. Biomarkers will help identify patients with PD and depression earlier in the future.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo/tratamento farmacológico , Doença de Parkinson/patologia , Biomarcadores/metabolismo , Citocinas/metabolismo , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/etiologia , Exercício , Humanos , Inibidores da Monoaminoxidase/uso terapêutico , Neurotransmissores/metabolismo , Doença de Parkinson/complicações , Inibidores de Captação de Serotonina/uso terapêutico
6.
Clin Neuropharmacol ; 42(4): 123-130, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31045589

RESUMO

OBJECTIVES: The aim of this open-label study was to investigate the long-term safety and efficacy of selegiline as monotherapy in Japanese patients with early Parkinson disease (PD). METHODS: We conducted a 56-week prospective study in patients with early PD (N = 134) who had previously completed the randomized, double-blind, placebo-controlled phase III trial of selegiline monotherapy for 12 weeks. In the present study, dosing was titrated from 2.5 to 10 mg/d in increments of 2.5 mg/d for 2 weeks. From the seventh week, the dosage was maintained at 10 mg/d until week 56. The primary outcome was any change in the total Unified Parkinson's Disease Rating Scale (UPDRS) score (part I + II + III) from baseline. Secondary outcomes, including changes in the UPDRS subscores and safety profile, were also evaluated. RESULTS: Ninety-one (67.9%) patients completed the 56-week study. Treatment with selegiline significantly reduced total UPDRS score from week 4 (mean ± SD, -2.62 ± 3.83; P < 0.0001) to week 56 (-3.39 ± 9.27; P < 0.01). The peak effect was seen at week 20 (-5.79 ± 5.57; P < 0.0001). In addition, we found similar improvements in the UPDRS parts II and III scores. The incidence rate of adverse drug reactions was 44.3% (58 patients) and did not increase during the period of 10 mg selegiline administration. CONCLUSIONS: Long-term monotherapy with selegiline (10 mg/d) was effective and well tolerated in patients with early PD in this 56-week study.


Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Selegilina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Escala de Avaliação Comportamental , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/administração & dosagem , Estudos Prospectivos , Selegilina/administração & dosagem
7.
Molecules ; 24(10)2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31130597

RESUMO

Gliomas are malignant brain tumors characterized by rapid spread and growth into neighboring tissues and graded I-IV by the World Health Organization. Glioblastoma is the fastest growing and most devastating IV glioma. The aim of this paper is to evaluate the biological effects of two potent and selective Monoamine Oxidase B (MAO-B) inhibitors, Cmp3 and Cmp5, in C6 glioma cells and in CTX/TNA2 astrocytes in terms of cell proliferation, apoptosis occurrence, inflammatory events and cell migration. These compounds decrease C6 glioma cells viability sparing normal astrocytes. Cell cycle analysis, the Mitochondrial Membrane Potential (MMP) and Reactive Oxygen Species (ROS) production were detected, revealing that Cmp3 and Cmp5 induce a G1 or G2/M cell cycle arrest, as well as a MMP depolarization and an overproduction of ROS; moreover, they inhibit the expression level of inducible nitric oxide synthase 2, thus contributing to fatal drug-induced oxidative stress. Cmp5 notably reduces glioma cell migration via down-regulating Matrix Metalloproteinases 2 and 9. This study demonstrated that our novel MAO-B inhibitors increase the oxidative stress level resulting in a cell cycle arrest and markedly reduces glioma cells migration thus reinforcing the hypothesis of a critical role-played by MAO-B in mediating oncogenesis in high-grade gliomas.


Assuntos
Antineoplásicos/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transformação Celular Neoplásica/efeitos dos fármacos , Citometria de Fluxo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Monoaminoxidase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo
8.
J Affect Disord ; 250: 199-203, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30861462

RESUMO

OBJECTIVES: Antidepressants may be less effective in treatment-resistant depression (TRD). In this exploratory study, we examined the widely held hypothesis that monoamine oxidase inhibitor (MAOI) therapy may be superior to tricyclic antidepressant (TCA) therapy for TRD. We also examined the influence of the number of prior treatment trials on TCA versus MAOI effectiveness in TRD. METHODS: Data were retrospectively extracted from approximately 2,500 treatment charts of patients with TRD who were attending a university mood disorder clinic between 1983 and 2015. Hierarchical linear modeling was used to examine the efficacy of drug class on outcome as well as the interaction between drug class and the number of prior antidepressant trials. RESULTS: 147 treatment outcome observations were made from 94 unipolar, depressed patients who either received TCA (N = 47) or MAOI (N = 100) monotherapy for TRD. For patients unresponsive to at least one prior trial, drug class significantly predicted end-of-treatment CGI/S scores, with TCAs showing worse (i.e., higher) end-of-treatment CGI/S scores relative to MAOI therapy (b = 1.04, t = 4.98, p < 0.0001). When examining the interaction between drug class and the number of prior antidepressant trials, the interaction effect was significant (b = -0.50, t = -2.43, p = 0.02); however, the advantage for MAOI versus TCA therapy decreases with more prior, failed, antidepressant trials. CONCLUSION: Results suggest that MAOIs may be more effective than TCAs for early stage TRD. This difference in effectiveness between MAOIs and TCAs diminished as the number of prior treatment trials increased. However, the TCA sample size was limited and the analysis was retrospective with non-randomized conditions.


Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Inibidores da Monoaminoxidase/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
9.
Pak J Pharm Sci ; 32(1(Special)): 371-375, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30852472

RESUMO

The present study designed to investigate the effect of monoamine oxidase inhibitor in the rat model of Coronary heart disease (cardiac hypertrophy). A total of 40 male adult Wistar rats having body weight 300-400 gram were equally distributed in two groups (Test group: Rats with Angiotensin II + monoamine oxidase inhibitor (Befloxatone); Reference group: Rats with cardiac hypertrophy induced by Angiotensin II). Rat model of cardiac hypertrophy were induced by Angiotensin II. Effect of Befloxatone on cardiac hypertrophy was evaluated by electrocardiography, hemodynamic and histological assessment. Vital signs such as pulse rate, and blood pressure were measured. Echocardiographic related variable including ejection fraction were also assessed in both the groups. Also, expression of monoamine oxidase was analyzed using by real-time-PCR and Western blot analysis. In results, we found following 1) monoamine oxidase inhibitor treatment prevents Angiotensin II induced increase in level of ANP and ßeta-myosin, which are responsible for inducing cardiac hypertrophic responses; 2) monoamine oxidase inhibitor ameliorates Angiotensin II induced cell enlargement by reducing the surface area of cells; 3) monoamine oxidase inhibitor attenuates the hypertrophic response triggered by Angiotensin II; 4) monoamine oxidase inhibitor ameliorates increased heart rate and average arterial pressure induced by angiotensin II; 5) Overall finding suggested that monoamine oxidase inhibitor improves left ventricle hypertrophy and ejection fraction by inhibiting monoamine oxidase enzyme in heart. The finding of this study gives the new vision to cardiovascular researchers to develop anti- hypertrophy therapy based on monoamine oxidase inhibition.


Assuntos
Cardiomegalia/tratamento farmacológico , Inibidores da Monoaminoxidase/uso terapêutico , Oxazóis/uso terapêutico , Angiotensina II , Animais , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Masculino , Inibidores da Monoaminoxidase/administração & dosagem , Miocárdio/patologia , Oxazóis/administração & dosagem , Ratos Wistar
10.
Molecules ; 24(3)2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30678358

RESUMO

Monoamine oxidase inhibitions are considered as important targets for the treatment of depression, anxiety, and neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. This has encouraged many medicinal chemistry research groups for the development of most promising selective monoamine oxidase (MAO) inhibitors. A large number of plant isolates also reported for significant MAO inhibition potential in recent years. Differently substituted flavonoids have been prepared and investigated as MAO-A and MAO-B inhibitors. Flavonoid scaffold showed notable antidepressant and neuroprotective properties as revealed by various and established preclinical trials. The current review made an attempt to summarizing and critically evaluating the new findings on the quercetin and related flavonoid derivatives functions as potent MAO isoform inhibitors.


Assuntos
Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Quercetina/química , Quercetina/farmacologia , Animais , Fenômenos Químicos , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/etiologia , Transtornos Mentais/metabolismo , Modelos Moleculares , Inibidores da Monoaminoxidase/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/metabolismo , Quercetina/uso terapêutico , Relação Estrutura-Atividade
11.
ACS Chem Neurosci ; 10(1): 252-265, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30296051

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder with multifactorial pathogenesis. Monoamine oxidase (MAO) and acetylcholinesterase enzymes (AChE) are potential targets for the treatment of AD. A total of 15 new propargyl containing 4,6-diphenylpyrimidine derivatives were synthesized and screened for the MAO and AChE inhibition activities along with ROS production inhibition and metal-chelation potential. All the synthesized compounds were found to be selective and potent inhibitors of MAO-A and AChE enzymes at nanomolar concentrations. VB1 was found to be the most potent MAO-A and BuChE inhibitor with IC50 values of 18.34 ± 0.38 nM and 0.666 ± 0.03 µM, respectively. It also showed potent AChE inhibition with an IC50 value of 30.46 ± 0.23 nM. Compound VB8 was found to be the most potent AChE inhibitor with an IC50 value of 9.54 ± 0.07 nM and displayed an IC50 value of 1010 ± 70.42 nM against the MAO-A isoform. In the cytotoxic studies, these compounds were found to be nontoxic to the human neuroblastoma SH-SY5Y cells even at 25 µM concentration. All the compounds were found to be reversible inhibitors of MAO-A and AChE enzymes. In addition, these compounds also showed good neuroprotective properties against 6-OHDA- and H2O2-induced neurotoxicity in SH-SY5Y cells. All the compounds accommodate nicely to the hydrophobic cavity of MAO-A and AChE enzymes. In the molecular dynamics simulation studies, both VB1 and VB8 were found to be stable in the respective cavities for 30 ns. Thus, 4,6-diphenylpyrimidine derivatives can act as promising leads in the development of dual-acting inhibitors targeting MAO-A and AChE enzymes for the treatment of Alzheimer's disease.


Assuntos
Acetilcolinesterase/metabolismo , Doença de Alzheimer/enzimologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacologia , Inibidores da Monoaminoxidase/síntese química , Monoaminoxidase/metabolismo , Pirimidinas/síntese química , Doença de Alzheimer/tratamento farmacológico , Linhagem Celular Tumoral , Inibidores da Colinesterase/uso terapêutico , Humanos , Inibidores da Monoaminoxidase/uso terapêutico , Pirimidinas/uso terapêutico , Relação Estrutura-Atividade
12.
Curr Neuropharmacol ; 17(9): 861-873, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30160213

RESUMO

Three inhibitors of type-B monoamine oxidase (MAOB), selegiline, rasagiline, and safinamide, are used for the treatment of Parkinson's disease (PD). All three drugs improve motor signs of PD, and are effective in reducing motor fluctuations in patients undergoing long-term L-DOPA treatment. The effect of MAOB inhibitors on non-motor symptoms is not uniform and may not be class-related. Selegiline and rasagiline are irreversible inhibitors forming a covalent bond within the active site of MAOB. In contrast, safinamide is a reversible MAOB inhibitor, and also inhibits voltage- sensitive sodium channels and glutamate release. Safinamide is the prototype of a new generation of multi-active MAOB inhibitors, which includes the antiepileptic drug, zonisamide. Inhibition of MAOB-mediated dopamine metabolism largely accounts for the antiparkinsonian effect of the three drugs. Dopamine metabolism by MAOB generates reactive oxygen species, which contribute to nigro-striatal degeneration. Among all antiparkinsonian agents, MAOB inhibitors are those with the greatest neuroprotective potential because of inhibition of dopamine metabolism, induction of neurotrophic factors, and, in the case of safinamide, inhibition of glutamate release. The recent development of new experimental animal models that more closely mimic the progressive neurodegeneration associated with PD will allow to test the hypothesis that MAOB inhibitors may slow the progression of PD.


Assuntos
Antiparkinsonianos/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Alanina/análogos & derivados , Alanina/uso terapêutico , Benzilaminas/uso terapêutico , Dopaminérgicos/uso terapêutico , Humanos , Indanos/uso terapêutico , Levodopa/uso terapêutico , Masculino , Selegilina/uso terapêutico
13.
Anatol J Cardiol ; 21(1): 39-45, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30587705

RESUMO

OBJECTIVE: The molecular pathway leading to myocardial cellular destruction after acute volume overload (AVO) may include monoamine oxidases. The aim of the present study was to investigate whether moclobemide (Mo), a monoamine oxidase inhibitor, protects the myocardium after AVO. METHODS: Sixty syngeneic Fischer rats underwent surgical abdominal aortocaval fistula to induce AVO. Eighteen rats were treated with Mo 10 mg/kg/day and were compared with 42 untreated rats with AVO without treatment. Myocardial recovery was analyzed using quantitative reverse transcription polymerase chain reaction for hypoxia-inducible factor 1-alpha, inducible nitric oxide synthase, interleukin 6, E-selectin, atrial natriuretic peptide (ANP), brain natriuretic peptide, vascular endothelial growth factor-alpha, matrix metalloproteinase 9, chitinase 3-like protein (YKL-40), and transforming growth factor-beta. RESULTS: After 3 days, the relative number of ischemic intramyocardial arteries in the left ventricle was lower in AVO treated with Mo than in without [0.04 (0.02-0.07) vs. 0.09 (0.07-0.14), point score unit]. After 1 day, ANP was lower in AVO treated with Mo than in without [0.95 (0.37-1.84) vs. 2.40 (1.33-3.09), fold changes from the baseline (FC), p=0.044], whereas after 1 and 3 days, YKL-40 was higher in AVO treated with Mo than in without [22.66 (14.05-28.83) vs. 10.06 (6.23-15.02), FC, p=0.006 and 6.03 (4.72-7.18) vs. 3.70 (2.62-5.35), FC, p=0.025]. CONCLUSION: Mo decreases intramyocardial arterial ischemia of the left ventricle after AVO while increases YKL-40, reflecting cellular protection during early cardiac remodeling. In the future, adding Mo may be a simple means for myocardial protection after AVO.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Moclobemida/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Miocárdio/metabolismo , Substâncias Protetoras/uso terapêutico , Animais , Fator Natriurético Atrial/metabolismo , Modelos Animais de Doenças , Moclobemida/administração & dosagem , Inibidores da Monoaminoxidase/administração & dosagem , Reação em Cadeia da Polimerase , Substâncias Protetoras/administração & dosagem , Ratos , Ratos Endogâmicos F344
14.
Biomater Sci ; 7(1): 296-306, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30468220

RESUMO

The development of versatile antitumor agents with tumor-imaging, targeting and therapeutic activity is promising for clinical cancer therapy. Prostate cancer is still the one of the leading threats to males. Current therapies have restricted clinical efficiency for patients with advanced and metastatic prostate cancer. Recent studies demonstrate that monoamine oxidase A (MAOA) levels elevate with prostate cancer aggression and metastasis. In addition, MAOA inhibitor therapies have been reported as an effective means to reduce the metastasis of prostate cancer and extend mouse survival. Thus, these findings provide evidence that MAOA is promising for the treatment of metastatic and advanced prostate cancer. Herein, three isoniazid (INH)-dye conjugates were synthesized by conjugating MAOA inhibitor INH with mitochondria-targeting NIRF heptamethine dyes to improve the therapeutic efficacy of prostate cancer. These INH-dye conjugates could accumulate in PC-3 cellular mitochondria via organic anion transport peptide (OATP), increase ROS generation, and induce cancer cells apoptosis. In prostate cancer bearing xenografts, INH-dye conjugates showed significantly improved tumor-homing characteristics, resulting in potent antitumor activity via a reduction in MAOA activity. These results suggest that INH-dye conjugates have great potential to be used as versatile antitumor agents with prostate cancer targeting, NIR imaging, and potent antitumor efficacy.


Assuntos
Antituberculosos/química , Antituberculosos/uso terapêutico , Isoniazida/análogos & derivados , Isoniazida/uso terapêutico , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Animais , Antituberculosos/farmacologia , Corantes/química , Corantes/farmacologia , Corantes/uso terapêutico , Reposicionamento de Medicamentos/métodos , Humanos , Isoniazida/farmacologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Células PC-3 , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
15.
J Neural Transm (Vienna) ; 125(11): 1719-1733, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30341696

RESUMO

In early 1920s, tyramine oxidase was discovered that metabolized tyramine and in 1933 Blaschko demonstrated that this enzyme also metabolized adrenaline, noradrenaline and dopamine. Zeller gave it the name monoamine oxidase (MAO) to distinguish it from the enzyme that oxidatively deaminated diamines. MAO was recognized as an enzyme of crucial interest to pharmacologists because it catalyzed the major inactivation pathway for the catecholamines (and, later, 5-hydroxytryptamine, as well). Within the few decade, the inhibitors of MAO were discovered and introduced for the treatment of depressive illness which was established clinically. However, the first clinical use exposed serious side effects, pharmacological interest in, and investigation of, MAO continued, resulting in the characterization of two forms, distinct forms, MAO-A and -B, and selective inhibitors for them. Selective inhibitors of MAO-B (selegiline, rasagiline and safinamide) have found a therapeutic role in the treatment of Parkinson's disease and reversible inhibitors of MAO-A offered antidepressant activity without the serious side effects of the earlier nonselective MAO inhibitors. Subsequent molecular pharmacological have also generated the concept of neuroprotection, reflecting the possibility of slowing, halting and maybe reversing, neurodegeneration in Parkinson's or Alzheimer's diseases. Increased levels of oxidative stress through the accumulation of iron in the Parkinsonian and Alzheimer brains has been suggested to be critical for the initiation and progress of neurodegeneration. Selective inhibition of brain MAO could contribute importantly to lowering such stress, preventing the formation of hydrogen peroxide. Interaction of Iron with hydrogen peroxide and lead to Fenton reaction and production of the most reactive radical, namely hydroxyl radical. There are complex interactions between free iron levels in brain and MAO, and cascade of neurotoxic events may have practical outcomes for depressive disorders and neurodegenerative diseases. As consequence recent novel therapeutic drugs for neurodegenerative diseases has led to the development of multi target drugs, that possess selective brain MAO A and B inhibitory moiety, iron chelating and antioxidant activities and the ability to increase brain levels of endogenous neurotrophins, such as BDNF, GDNF VEGF and erythropoietin and induce mitochondrial biogenesis.


Assuntos
Transtorno Depressivo/tratamento farmacológico , Quelantes de Ferro/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doenças Neurodegenerativas/tratamento farmacológico , Animais , Humanos
16.
Int J Mol Sci ; 19(10)2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-30257452

RESUMO

Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models.


Assuntos
Inibidores da Monoaminoxidase/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/etiologia , Fenelzina/uso terapêutico , Sacarose/efeitos adversos , Tecido Adiposo Branco/efeitos dos fármacos , Tecido Adiposo Branco/metabolismo , Adiposidade/efeitos dos fármacos , Administração Oral , Animais , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos não Esterificados/metabolismo , Lipogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibidores da Monoaminoxidase/administração & dosagem , Obesidade/sangue , Obesidade/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenelzina/administração & dosagem , Sacarose/metabolismo , Ganho de Peso/efeitos dos fármacos
17.
J Neurol Sci ; 393: 1-3, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30077942

RESUMO

Concurrent use of modafinil or armodafinil with monoamine oxidase inhibitors (MAOIs) is contraindicated due to a theoretical risk of drug synergism and acute hypertensive episodes. However, few data are available to substantiate that risk, and several case studies have suggested that the combination is safe. To our knowledge, we present the first case of a patient treated concurrently with armodafinil and tranylcypromine. The patient developed an acute hypertensive crisis with severe headache, nausea, blurry vision, and neck stiffness. Her symptoms corresponded with the predicted pharmacokinetic and pharmacodynamic response. She was also taking brexpiprazole, which could have contributed to her underlying symptoms. However, limited data suggest that the single combination of brexpiprazole with armodafinil or MAOIs would be safe. Upon review of the literature, two out of seven patients, including our own, treated concurrently with modafinil or armodafinil and an MAOI developed an adverse reaction. Physicians should exercise caution if using these classes of drugs together.


Assuntos
Cefaleia/etiologia , Hipertensão/etiologia , Modafinila/efeitos adversos , Inibidores da Monoaminoxidase/efeitos adversos , Tranilcipromina/efeitos adversos , Promotores da Vigília/efeitos adversos , Adulto , Sinergismo Farmacológico , Quimioterapia Combinada/efeitos adversos , Feminino , Cefaleia/terapia , Humanos , Hipertensão/terapia , Modafinila/farmacocinética , Modafinila/uso terapêutico , Inibidores da Monoaminoxidase/farmacocinética , Inibidores da Monoaminoxidase/uso terapêutico , Tranilcipromina/farmacocinética , Tranilcipromina/uso terapêutico , Promotores da Vigília/farmacocinética , Promotores da Vigília/uso terapêutico
18.
Fortschr Neurol Psychiatr ; 86(10): 624-634, 2018 10.
Artigo em Alemão | MEDLINE | ID: mdl-30142650

RESUMO

AIM: Safinamide (Xadago®) is a newly approved selective MAO-B inhibitor for the treatment of Parkinson's Disease (PD). The X-TRA study investigated the efficacy and tolerability of the substance under clinical practice conditions. METHODS: Prospective, observational study in unselected patients in line with safinamide product specifications. RESULTS: Of the 299 patients included (65.9 % males, age 72.7 ± 9.0 years, duration of disease 7.8 ± 5.9 years), at the beginning of the documentation 229 patients (81.2 %) received L-dopa, 108 (39.3 %) combination drugs containing L-dopa, 172 (59.3 %) a dopamine agonist and 23 (8.3 %) a COMT inhibitor. Of these, 203 patients were followed-up over a period of 6 months. The MDS-UPDRS Part III score for motor symptoms decreased from a baseline value of 48.2 ± 22.1 points by 6.8 ± 14.5 points at the end of the study. The Non-Motor Symptoms Scale score indicating the presence or absence of motor symptoms decreased from a baseline value of 57.6 ± 42.1 by 9.3 ± 2.1 points, the Abnormal Involuntary Movement Score from 4.6 ± 5.8 points by 0.9 ± 2.7 points.The Parkinson's Disease Score (PDQ-8) for assessing quality of life decreased from a baseline value of 39.4 ± 18.2 points by 4.3 ± 13.7 points, reflecting an improvement. In total, 300 adverse events were classified as related to safinamide in 132 patients (44.1 %). Fifty-three events were serious (in 15 patients; 5 %). Seventy-four patients (24.7 %) discontinued safinamide therapy because of adverse drug reactions. CONCLUSIONS: Safinamide therapy improved the motor and non-motor symptoms as well as the quality of life in PD. Most patients tolerated the therapy well. The only side effects that occurred are those described in the patient information leaflet.


Assuntos
Alanina/análogos & derivados , Antiparkinsonianos/uso terapêutico , Benzilaminas/uso terapêutico , Levodopa/uso terapêutico , Inibidores da Monoaminoxidase/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina/efeitos adversos , Alanina/uso terapêutico , Antiparkinsonianos/efeitos adversos , Benzilaminas/efeitos adversos , Avaliação da Deficiência , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Levodopa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Inibidores da Monoaminoxidase/efeitos adversos , Doença de Parkinson/fisiopatologia , Estudos Prospectivos
19.
J Med Chem ; 61(15): 6937-6943, 2018 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-29969030

RESUMO

Contilisant, a permeable, antioxidant, and neuroprotectant agent, showing high nM affinity at H3R and excellent inhibition of the monoamine oxidases and cholinesterases, is an affine and selective S1R agonist in the nanomolar range, based on the binding affinity and functional experiment, a result confirmed by molecular modeling. In addition, contilisant significantly restores the cognitive deficit induced by Aß1-42 in the radial maze assay in an in vivo Alzheimer's disease test, comparing very favorably with donepezil.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Colinesterases/metabolismo , Antagonistas dos Receptores Histamínicos/farmacologia , Indóis/farmacologia , Inibidores da Monoaminoxidase/farmacologia , Monoaminoxidase/metabolismo , Piperidinas/farmacologia , Receptores Histamínicos/metabolismo , Receptores sigma/agonistas , Doença de Alzheimer/enzimologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/química , Animais , Antagonistas dos Receptores Histamínicos/uso terapêutico , Indóis/uso terapêutico , Camundongos , Inibidores da Monoaminoxidase/uso terapêutico , Fragmentos de Peptídeos/química , Piperidinas/uso terapêutico , Multimerização Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína , Memória Espacial/efeitos dos fármacos
20.
Expert Opin Pharmacother ; 19(10): 1057-1070, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30056792

RESUMO

INTRODUCTION: Generalized anxiety disorder (GAD) often begins during adolescence or early adulthood and persists throughout the lifespan. Randomized controlled trials support the efficacy of selective serotonin and selective serotonin norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively), as well as benzodiazepines, azapirones, anti-adrenergic medications, melatonin analogs, second-generation antipsychotics, kava, and lavender oil in GAD. However, psychopharmacologic treatment selection requires clinicians to consider multiple factors, including age, co-morbidity, and prior treatment. Areas covered: The authors review the literature concerning pharmacotherapy for pediatric and adult patients with GAD with specific commentary on the efficacy and tolerability of selected agents in these age groups. The authors describe an algorithmic approach to the pediatric and adult patient with GAD and highlight considerations for the use of selected medications in these patients. Expert opinion: In adults with GAD, SSRIs and SNRIs represent the first-line psychopharmacologic treatment while second-line pharmacotherapies include buspirone, benzodiazepines, SGAs, and pregabalin. In pediatric patients with GAD, SSRIs should be considered the first line pharmacotherapy and psychotherapy enhances antidepressant response.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Inibidores de Captação de Serotonina/uso terapêutico , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico , Adulto , Antidepressivos/uso terapêutico , Antipsicóticos/uso terapêutico , Transtornos de Ansiedade/patologia , Criança , Prática Clínica Baseada em Evidências , Humanos , Inibidores da Monoaminoxidase/uso terapêutico
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