Effects of in vitro amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts

Abstract Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.

Pharmacological and Neuromodulatory Treatments for Panic Disorder: Clinical Trials from 2010 to 2018

OBJECTIVE: Treatment for panic disorder (PD) have evolved, although there is still a strong unmet need for more effective and tolerable options. The present study summarizes and discusses recent evidence regarding the pharmacological and neuromodulatory treatment of PD. METHODS: MEDLINE, Cochrane Library, PsycINFO and Thomson Reuters’s Web of Science were searched for clinical trials published between 2010 and 2018. We included all prospective experimental studies including randomized controlled trials (RCT) and other clinical trials with more than 10 patients. RESULTS: Only 11 articles met the inclusion criteria, including 4 RCT, 3 open clinical trials and 5 comparative clinical trials. RCT demonstrated efficacy of transcranial magnetic stimulation (TMS) in only one of two trials. Neither pindolol nor d-fenfluramine were effective in blocking flumazenil-induced panic attacks. Augmentation with quetiapine was not superior to placebo. Open trials indicated that escitalopram, vortioxetine and TMS may be effective. Comparative trials did not demonstrate superiority from any drug, but confirmed tranylcypromine, paroxetine, clonazepam and alprazolam as effective options. CONCLUSION: The current study confirmed the efficacy of tranylcypromine, paroxetine, clonazepam, alprazolam and escitalopram. Vortioxetine and TMS, with duration of 4 or more weeks, also seems to be effective. Quetiapine, pindolol and d-fenfluramine were not considered effective compounds.

Effect of monoamine oxidase inhibitor on the differentiation of malignant glioma cell / 生物医学工程学杂志

To investigate the effect of monoamine oxidase inhibitor tranylcypromine (TCP) on the differentiation of human U251 glioma cells, we treated U251 cells with TCP and/or 100 nmol/L histone deacetylase inhibitor trychostatin A (TSA). The differentiation of U251 cells was observed with inverted microscopy. The cell proliferation and cell cycle distribution were determined by MTT assay and flow cytometry, respectively. Apoptosis was observed by Hoechst 33258 staining. The levels of differentiation-related genes were assessed by real-time PCR and Western blotting. TCP-induced differentiation was characterized by typical morphological changes, inhibition of cellular proliferation, accumulation of cells in the G1 phase of the cell cycle, decreased expression of the pluripotency transcription factors Oct4 and Sox2, and increased expression of glial fibrillary acid protein (GFAP). The combination of TCP and TSA treatment also triggered an over-expression of GFAP. These findings suggest that TCP may induce differentiation of U251 glioma cells, and the differentiation process may be promoted by histone deacetylase inhibitor TSA.

MAO-inhibitors in Parkinson's Disease

Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD.

Monoamine Oxidase Inhibitors Attenuate Cytotoxicity of 1-Methyl-4-phenylpyridinium by Suppressing Mitochondrial Permeability Transition

Mitochondrial permeability transition has been shown to be involved in neuronal cell death. Mitochondrial monoamine oxidase (MAO)-B is considered to play a part in the progress of nigrostriatal cell death. The present study examined the effect of MAO inhibitors against the toxicity of 1-methyl-4-phenylpyridinium (MPP+) in relation to the mitochondrial permeability transition. Chlorgyline (a selective inhibitor of MAO-A), deprenyl (a selective inhibitor of MAO-B) and tranylcypromine (non-selective inhibitor of MAO) all prevented cell viability loss, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH in differentiated PC12 cells treated with 500 micrometer MPP+. The MAO inhibitors at 10 micrometer revealed a maximal inhibitory effect and beyond this concentration the inhibitory effect declined. On the basis of concentration, the inhibitory potency was tranylcypromine, deprenyl and chlorgyline order. The results suggest that chlorgyline, deprenyl and tranylcypromine attenuate the toxicity of MPP+ against PC12 cells by suppressing the mitochondrial permeability transition that seems to be mediated by oxidative stress.

Metabolic kinetics of MN9202 in Beagle dog liver microsomes / 药学学报

<p><b>AIM</b>To study the metabolic kinetics of MN9202 in Beagle dog liver microsome.</p><p><b>METHODS</b>Beagle dog liver microsomes were prepared by using ultracentrifuge method. After incubating 0.4 micromol x L(-1) MN9202 with 1 g x L(-1) microsomes for 30 min at 37 degrees C, the reaction was terminated by adding 0.5 mL alkalization. The RP-HPLC was used to determine the drug in the incubation mixture. The Michaelis-Menten parameters Km, and Vmax in Beagle dog liver microsomes were initially estimated by analyzing Lineweave-Brurk plot. Various selective CYP inhibitors were used to investigate their inhibitory effect on the metabolism of MN9202.</p><p><b>RESULTS</b>The Km, Vmax and CLint of MN9202 were (22.6 +/- 8.0) micromol x L(-1), (0.54 +/- 0.17) micromol x g(-1) x min(-1) and (0.0242 +/- 0.0009) L x g(-1) x min(-1), respectively. The metabolism of MN9202 was significantly inhibited by ketoconazole (Ket) and troleandomycin (Tro) in Beagle dog liver microsomes. Tranylcypromine (Tra) could inhibit the metabolism of drug as well. While other inhibitors showed little inhibitory effect on the metabolism of MN9202.</p><p><b>CONCLUSION</b>It was shown that CYP3A and CYP2C19 were involved in MN9202 metabolism. The inhibitors of human CYP3A and CYP2C19 may have potential interaction with MN9202, and this can reduce the metabolism rate and increase the toxicity of MN9202.</p>

Beneficial Effects of High-Dose Transamine on Hematologic Aspects in Cardiopulmonary Bypass / 대한흉부외과학회지

BACKGROUND: The purpose of this study was to independently evaluate the beneficial effects of a high dose of transamine administrated prior to CPB on the postoperative hematologic aspect and bleeding. MATERIALS AND METHODS: This study included randomly selected groups of 40 adult patients undergoing OHS with CPB. All patients were divided into 2 groups: transamine group (T-group, n=20) and placebo group (P-group, n=20). The T-group received a high-dose of transamine (10 g) before and during CPB. The P-group received normal saline at the same times and served as a control group. RESULTS: The results of comparative studies between the 2 groups in the same hematologic variables were summarized as follows. (1) During CPB, the fibrinogen concentrations and platelet counts were significantly lower in the P-group than in the T-group (p<0.01). (2) During CPB, production of D-dimer occurred in 18 patients (90%) in the P-group and did not occur in the T-group (0%) (p<0.0001). (3) At CPB-off, the % concentration of fibrinogen (70.2+/-3.9%) and the % platelet counts (72.4+/-4.5%) of the T-group were significantly higher than those (54.5+/-3.8%, 64.3+/-2.9%) of the P-group (p<0.01). (4) Postoperative values of PT (14.0+/-0.03 sec.) and aPTT (27.6+/-0.1 sec.) of the T-group were significantly lower than those (16.0+/-0.02sec., 30.1+/-0.1sec.) of the P-group (p<0.05). (5) Postoperative bleeding and requirement of whole blood and other blood products were significantly less in the T-group than in the P-group (p <0.05). (6) There were no significant hypercoagulability signs such as cerebral em bolism, myocardial infarction, pulmonary embolism, or any other neurological prob lems in either group. CONCLUSIONS: We concluded that a high dose of transamine administered prior to CPB prevents the activation of fibri nolytic system and has beneficial effects of reducing the postoperative bleeding t endency without apparent hypercoagulability signs.

Crise hipertensiva espontânea durante o uso de IMAO: relato de caso e revisäo da literatura / Spontaneous hypertensive crises during a the use of MAOIs: Clinical case and literature review

Os inibidores da monoaminixidase säo indicados para o tratamento de diversos transtornos psiquiátricos, principalmente os de ansiedade e depressäo. O risco de episódios hipertensivos é inferior a 1 por cento. Alguns pacientes que utilizam IMAOS näo seletivos apresentam episódios hipertensivos espontâneos, i.e., näo desencadeados por transgressöes alimentares ou medicamentosas. Relatamos um caso de crise hipertensiva espontânea induzida pela tranilcipromina e fazemos uma revisäo da literatura. Há um total de 12 casos descritos em sete artigos diferentes. Discutimos a possível fisiopatologia, os fatores de risco e o manejo clínico. Säo necessárias mais investigações para compreensäo deste fenômeno

Psicoterapia cognitiva e comportamental do transtorno do pânico e da agorafobia como uma alternativa eficaz e crítica aos tratamentos biológicos / Cognitive and behavorial psychotherapy of panic disorder and agoraphobia as an effective and critical therapeutic alternative to biological approaches to treatment

Modelos etiólogicos e estratégias de tratamento cognitivas e comportamentais para o transtorno do pânico e da agarafobia são revistos. Uma discussão dos problemas epidemiológicos e clínicos associados a uma opção por: (1) um enfoque biológico que enfatiza apenas tratamentos farmacológicos; ou por (2) um enfoque psicológico que valoriza apenas tratamentos psicoterapêuticos é realizada, apontando para a necessidade de uma definição mais precisa da natureza destes transtornos e de seus tratamentos, tendo em vista as implicações de longo prazo, quando se busca uma remissão pura e simples da ansiedade. Defende-se a idéia de que a investigação cinetífica em um ou outro nível é igualmente relevante e irredutível; e que a escolha de uma ou outra estratégia de tratamento se dê por fatores específicos do problema de cada paciente mais do que por uma tendenciosidade adquirida profissionalmente

Tratamento farmacológico da fobia social / The pharmacological treatment of social phobia

A fobia social é um transtorno crônico, sem grandes ou significativos períodos de remissao. Na fobia social generalizada a incapacitaçao é muito grande. O paciente fica extremamente limitado, quase nao consegue realizar atos corriqueiros, que envolvam algum contato social. Nesses casos o tratamento farmacológico contínuo deve ser firmemente indicado. Sem se perder de vista a tradicional relaçao risco-benefício. No programa de Ansiedade e Depressao do Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro, os IMAOs clássicos, fenelzine ou tranilcipromina, sao reservados para casos muitos graves e resistentes a outros tratamentos. Os mais eficazes e de efeito mais rápido sao o clonazepam ou tranilcipromina, apesar de inúmeros efeitos adversos. Para casos com incapacitaçao moderada a leve o caminho mais seguro quanto à tolerância é a moclobemida. Os inibidores seletivos da recaptação da serotonina - setralina, fluoxetina ou paroxetina - parecem ser boas opçoes para esses casos mais estudos sao necessários

Farmacoterapia do transtorno do pânico / Pharmacotherapy of panic disorders

A farmacoterapia dos transtornos ansiosos está sendo padronizada atualmente nos serviços psiquiátricos. Este artigo revisa a abordagem clínica da farmacoterapia do transtorno do pânico. Para tanto lança mao de dados da literatura recente edas evidências da experiência clínica, enfatizando importantes elementos de informaçao para o tratamento, reavalia a variedade das classes de psicofármacos e apresenta sugestoes para o tratamento de casos de pacientes resistentes.

Sobre o uso de I.M.A.O em um caso de transtorno obsessivo-compulsivo grave e refratário ao tratamento convencional / I.M.A.O. use in a case of acute and refractory obsessive-complusive disorder in the conventional treatment

Os autores do presente artigo discutem, a partir do relato de um caso atendido no Hospital de Clínicas de Porto Alegre (HCPA), alterantivas terapêuticas em casos graves e refratários de transtorno obsessivo-compulsivo (TOC). No presente caso, foi utilizado um inibidor da monoaminoxidase (IMAO) - tranilcipromina - no tratamento de um paciente já tratado com farmacoterapia convencional e sem resposta adequada. Por fim, säo descritos dados da literatura sobre os avanços da neuroanatomia funcional deste transtorno

Efeitos colaterais da tranilcipromina em 22 pacientes com transtornos do humor ou de ansiedade. Série Psicofarmacologia - 36 / Side effects of tranylcypromine in 22 patients with mood or anxiety disorders

Objetivo. A tranilcipromina é uma droga sabidamente eficaz no tratamento dos transtornos do humor e da ansiedade, embora muitas de suas particularidades no uso clínico ainda näo estejam satisfatoriamente esclarecidas. O presente trabalho objetiva descrever a natureza e a frequência dos principais efeitos colaterais da tranilcipromina e avaliar seu impacto no resultado final do tratamento. Pacientes e métodos. Vinte e dois pacientes com transtornos do humor ou de ansiedade foram tratados com tranilcipromina na dose de 5 a 80 mg/dia por um período de 20 dias a 22 meses. Os efeitos terapêuticos e adversos observados durante o tratamento foram descritos e analisados. Resultados. 100 por cento dos pacientes apresentaram efeitos colaterais de maior ou menor intensidade. Os principais efeitos adversos observados foram a sonolência (45 por cento dos pacientes), boca seca (41 por cento), hipotensäo postural (32 por cento), insônia (23 por cento), diminuiçäo da libido (23 por cento ) e disfunçäo erétil (18 por cento). Em apenas 36 por cento dos casos, a tranilcipromina mostrou-se eficiente e bem tolerada. Conclusöes. A tranilcipromina se revelou em nosso estudo uma droga de difícil manejo, com abundantes efeitos colaterais. É possível, contudo, que estes resultados reflitam as características clínicas da populaçäo estudada

A tranilcipromina no tratamento do transtorno obsessivoðcompulsivo: relato de seis casos / The tranylcypromine in the treatmente of obsessiveðcompulsive disorder: report of six cases

O transtorno obsessivoðcompulsivo (TOC) é uma doença grave e incapacitante que requer tratamento eficaz. Os fármacos usualmente utilizados com esta finalidade (inibidores de recaptação de serotonina) produzem melhora significativa em apenas cerca de metade dos pacientes. A tranilcipromina, um IMAO não seletivo, constituiðse numa alternativa ð pouco estudada ð de tratamento, principalmente quando estão associados sintomas fóbicos e ansiosos. Relatamos seis casos de TOC tratados com tranilcipromina. Quando pacientes responderam favoravelmente e dois não toleraram os efeitos colaterais da medicação, sendo esta retirada. Os IMAOs se apresentam como uma opção no tratamento de TOC

Programa de Ansiedade e Depressäo-UFRJ. Série Psicofarmacologia. 11: IMAOs no tratamento da depressäo do paciente idoso refratário / MAOIs in the treatment of depression of refractory geriatric patient

Os inibidores da monoaminoxidase (IMAOs), nos últimos 15 anos, vêm sendo reabilitados dentro da psiquiatria. Por exemplo, considera-se, atualmente, que sejam agentes de primeira linha na depressäo atípica, fobia social e nos pacientes resistentes ou refratários aos antidepressivos tricíclicos (ADTs). Há indicaçöes ainda controvertidas, tal como sua utilizaçäo no idoso, onde o próprio fabricante da tranilcipromina contra-indica seu uso. Contudo, a depressäo no idoso muitas vezes cursa com elevada morbidade-mortalidade, existindo também um grupo significativo de pacientes apresentando refratariedade ou intolerância aos efeitos indesejáveis de antidepressivos como os tricíclicos, o que justifica alternativas como os IMAOs. Fez-se revisäo da literatura sobre a eficácia e segurança dos IMAOs no paciente geriátrico deprimido, ilustrando com quatro casos tratados no Programa de Ansiedade e Depressäo - UFRJ. Localizaram-se quatro ensaios abertos e três duplos-cegos, controlados, todos com resultados favoráveis em termos de eficácia, constituindo a hipotensäo ortostática o efeito indesejável mais comum e mais trabalhoso. Conclui-se que os IMAOs podem ser tratamento seguro e eficaz nessa faixa etária, na medida em que os doentes sigam dieta com baixa concentraçäo de tiramina e evitem drogas simpaticomiméticas

Programa de Ansiedade e Depressäo-UFRJ. Série Psicofarmacolofia: 8. A tranilcipromina na prática psiquiátrica / Tranylcypromine in psychiatric practce

A tranilcipromina é uma droga eficaz e segura, uma vez obedecidas as restriçöes dietéticas e medicamentosas, podendo ser utilizada com vantagens nas depressöes bipolares, atípicas e geriátricas. É útil no tratamento das depressöes näo responsivas a antidepressores tricíclicos, associada ou näo ao carbonato de lítio. É eficaz nos ataques de pânico e na fobia social. Pode ser utilizada como alternativa no tratamento de pacientes com transtorno obsessivo-compulsivo, bulimia, personalidade borderline e em crianças com transtorno de déficit de atençäo com hiperatividade. O paciente deve ter bom nível de inteligência, disciplina e bom relacionamento com o médico assistente para que se garanta a aderência ao tratamento

Programa de Ansiedade e Depressäo-UFRJ. Série Psicofarmacologia: 1. Tratamento farmacológico do transtorno obsessivo-compulsivo / Pharmacological treatment of obsessive-compulsive disorder

Estudos epidemiológicos recentes demonstram que o transtorno obsessivo-compulsivo é muito mais frequente do que se pensava (2,5//). O transtorno é altamente incapacitante. A hipótese de uma etiologia "serotoninérgica", apesar de simplista, está sendo estuda. O diagnóstico é fácil e os sintomas evidentes. Na década de 80 passou-se a demonstrar que o transtorno obsessivo-compulsivo responde bastante bem a certos medicamentos, antidepressores "serotoninérgicos", clomipramina, ou inibidores da monoaminoxidase clássicos, tranilcipromina. Os efeitos terapêuticos maiores säo obtidos com doses altas - 300mg/dia de clomipramina ou 60mg/dia de tranilcipromina. A comprovaçäo da eficácia de medicamentos de 2ª geraçäo (fluoxetina ou moclobemida) ainda demanda maiores estudos. Os medicamentos induzem vários efeitos indesejáveis e as doses devem ser aumentadas lentamente. Estudos sobre o tratamento a longo prazo, com esses medicamentos, estäo em fase inicial, inclusive no Programa de Ansiedade e Depressäo do Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro

Tranylcypromine [MAOI] in attention deficit hyperactivity disorder in children

Tranylcypromine [MAOI] was administered to twenty seven children [mean age 7.4 years +/- 3.2] with DSM-III-R Attention Deficit Hyperactivity Disorder [ADHD]. Comparison of pre-and post-medication behavioral assessments using the Conners Abbreviated Hyperactivity Rating Scale showed a statistically significant difference [P< 0.001] which suggest that tranylcypromine could be an effective antihyperactivity drug

Does butorphanol produce interaction with monoamine oxidase inhibitors [tranylcypromine]? comparative experimental study with pethidine

This study demonstrated the possibility of the interaction between tranylcypromine and butorphanol compared with pethidine. The LD50 of pethidine and butorphanol were determined in mice pretreated either with nonselective monoamine oxidase [MAO] inhibitors, tranylcypromine orally for eight days or with saline orally. Tranylcypromine decreased the LD50 of both pethidine and butorphanol by 70% and 41%, respectively. Anesthetized rabbits with halothane pretreated either with tranylcypromine or saline were given pethidine 5 mg/kg iv or butorphanol 0.5, 1 and 2 mg/kg iv, pethidine produced a marked increase in blood pressure in rabbits pretreated with tranylcypromine and did not affect significantly the heart rate. However, butorphanol did not affect either blood pressure or heart rate at dose of 0.5 or 1 mg/kg, but the largest dose of butorphanol [2mg/kg] produced hypotension and tachycardia in rabbits pretreated with tranylcypromine. Neither pethidine nor butorphanol affected the temperature of anesthetized rabbits pretreated with tranylcypromine or saline