Amitriptyline, clomipramine, and maprotiline attenuate the inflammatory response by inhibiting neutrophil migration and mast cell degranulation

Objective: Despite the recognized anti-inflammatory potential of heterocyclic antidepressants, the mechanisms concerning their modulating effects are not completely known. Thus, we evaluated the anti-inflammatory effect of amitriptyline, clomipramine, and maprotiline and the possible modulating properties of these drugs on neutrophil migration and mast cell degranulation. Methods: The hind paw edema and air-pouch models of inflammation were used. Male Wistar rats were treated with saline, amitriptyline, clomipramine or maprotiline (10, 30, or 90 mg/kg, per os [p.o.]) 1 h before the injection of carrageenan (300 μg/0.1 mL/paw) or dextran (500 μg/0.1 mL/paw). Then, edema formation was measured hourly. Neutrophil migration to carrageenan (500 μg/pouch) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) (10-6 M/mL/pouch) was also investigated in 6-day-old air-pouch cavities. Compound 48/80-induced mast cell degranulation was assessed in the mesenteric tissues of antidepressant-treated rats. Results: All tested antidepressants prevented both carrageenan- and dextran-induced edema. The anti-inflammatory effect of these drugs partially depends on the modulation of neutrophil migration, since they significantly counteracted the chemotactic response of both carrageenan and fMLP (p < 0.01). Furthermore, amitriptyline, clomipramine and maprotiline inhibited compound 48/80-induced mast cell degranulation (p < 0.001). Conclusions: These results suggest an important anti-inflammatory role of heterocyclic antidepressants, which is dependent on the modulation of neutrophil migration and mast cell stabilization. .

Maprotiline treatment differentially influences cardiac β -adrenoreceptors expression under normal and stress conditions

Alterations in cardiac function were observed in antidepressants treated patients and published in several clinical reports. These detected changes could be either a consequence of the treatment or of depression itself, which has already been proved to be a risk factor in heart diseases. In order to determine a possible influence of chronic treatment with norepinephrinergic reuptake inhibitor, maprotiline, on the heart, we investigated gene expression of cardiac β-adrenoceptors both in controls and in animals with signs of depression. The rats were divided into two groups, unstressed controls and those exposed to chronic unpredictable mild stress (CUMS). The groups were further divided into two subgroups, one receiving daily intraperitoneal injections of vehicle (sterile water) and another one maprotiline (10 mg/kg) for four weeks. Tissue samples were collected after the last application. Gene expression of cardiac β1- and β2-adrenoceptor was determined using Real-time RT-PCR analysis. Our results show that in control animals expression of both adrenoreceptors was decreased in the right atria after 4 weeks of maprotiline application. Contrary, the same treatment led to a significant increase in expression of cardiac β1-adrenoceptor in the stressed rats, with no change in the characteristics of β2-adrenoceptor. Our findings might reflect the that molecular mechanisms are underlying factors involved in the development of cardiovascular diseases linked with antidepressant treatment.

Vários relatórios clínicos observaram alterações de funcionamento cardíaco de pacientes depressivos que foram tratados com os antidepressivos. As alterações detectadas podem ser consequência do tratamento ou, por outro lado, da depressão que, como se tem provado, é um fator de risco no caso de doenças cardíacas. De modo a determinar a possível influência de tratamento crônico com o inibidor da recaptação de norepinefrina, maprotilina, no coração, foi investigada a expressão do gene aos receptores β-adrenérgicos cardíacos dos animais em grupos de controle e em grupos com sinais de depressão. Os ratos foram divididos em grupos de controle não estressados e os grupos de ratos submetidos ao estresse crônico moderado imprevisível (CUMS). Os grupos foram, ainda, divididos em dois subgrupos, que, durante quatro semanas, diariamente receberam injeções intraperitoneais de placebo (água estéril) ou de maprotilina (10 mg/kg). As amostras de tecido foram coletadas após a última aplicação. A expressão do gene aos receptores adrenérgicos β1 e β2 foi determinada utilizando a análise PCR quantitativa em tempo real (RT-PCR). Os nossos resultados demonstram a diminuição de expressão dos ambos os receptores adrenérgicos no átrio direito dos animais do grupo de controle depois de quatro semanas de aplicação de maprotilina. Em contraste, o mesmo tratamento conduziu ao aumento significativo na expressão do receptor β1-adrenérgico no coração dos ratos estressados, sem qualquer alteração nas características do receptor β2-adrenérgico. Estes resultados podem refletir os mecanismos moleculares envolvidos no desenvolvimento de doenças cardiovasculares associadas ao tratamento com os antidepressivos.

Effect of glibenclamide on antinociceptive effects of antidepressants of different classes

OBJECTIVES: The purpose of this work was to determine whether the intraperitoneal administration of glibenclamide as a K ATP channel blocker could have an effect on the antinociceptive effects of antidepressants with different mechanisms of action. METHODS: Three antidepressant drugs, amitriptyline as a dual-action, nonselective inhibitor of noradrenaline and a serotonin reuptake inhibitor, fluvoxamine as a selective serotonin reuptake inhibitor and maprotiline as a selective noradrenaline reuptake inhibitor, were selected, and the effect of glibenclamide on their antinociceptive activities was assessed in male Swiss mice (25-30 g) using a formalin test. DISCUSSION: None of the drugs affected acute nociceptive responses during the first phase. Amitriptyline (5, 10 mg/ kg), maprotiline (10, 20 mg/kg) and fluvoxamine (20 and 30 mg/kg) effectively inhibited pain induction caused by the second phase of the formalin test. Glibenclamide (5 mg/kg) alone did not alter licking behaviors based on a comparison with the control group. However, the pretreatment of animals with glibenclamide (10 and 15 mg/kg) partially reversed the antinociceptive effects of fluvoxamine but not those of maprotiline. In addition, the highest dose of glibenclamide (15 mg/kg) partially prevented the analgesic effect of amitriptyline. CONCLUSION: Therefore, it seems that adenosine triphosphate-dependent potassium channels have a major role in the analgesic activity of amitriptyline and fluvoxamine.

[ effect of different doses of maprotiline on the treatment of Iranian patients suffering from moderate MDD]

Treatment effect of maprotiline at different doses [50-150 mg/d] as a tetracyclic antidepressant, with major effects on NEP and less anticholinergic side effects compared to some other tricyclic medications, has been compared with other medications. Given ethical and cultural differences as well as pharmacokinetic characteristics between Iranian populations, the current study was carried out to determine the effect of different doses of maprotiline in treatment of moderate MDD, its therapeutic ratio and related side effects in each dose, and also to define the effective dose of maprotiline. This quasi-experimental study was performed on the patients with moderate MDD who referred to psychiatry clinics. Thirty cases were selected from the patient with age between 25- 50 years, with 20

Clinical observation on effect of danzhi xiaoyao powder in treating depression / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect and side effect of Danzhi Xiaoyao powder (DXP) in treating depression.</p><p><b>METHODS</b>A randomized controlled and double-blinded study was conducted in 63 cases of depression by divided them into the western medicine group (WMG, 31 cases) treated with maprotiline, and the Chinese medicine group (CMG, 32 cases) treated with DXP. The effect of therapy was evaluated before and at the 2nd, 4th and 6th week of the treatment with Hamilton's depressive scale (HAMD), self-rating depression scale (SDS), self-rating anxiety scale (SAS) and the scale for TCM syndrome and symptom differentiation (TCM-SSD), and the side-effect of therapy was assessed with Asberg side-effect scale as well.</p><p><b>RESULTS</b>There was no significant difference between the two groups in scores of HAMD, SDS, SAS, and TCM-SSD. The markedly effective rate in CMG was 84% and in WMG 87%, showed no significance between them (P > 0.05). The scores of HAMD, SDS and SAS of both groups were remarkably lowered after therapy (P < 0.05). However, the score of Asberg in CMG was lower than that in WMG (P < 0.05).</p><p><b>CONCLUSION</b>DXP shows the effect equivalent to that of maprotiline, but with obviously less side-effect.</p>

Comparative observation on efficacy of jieyu pill and maprotiline in treating depression / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the clinical efficacy, adverse reaction and safety of Jieyu pill (JYP) in treating depression.</p><p><b>METHODS</b>The randomized controlled trial was conducted in 28 patients in the treated group and 29 patients in the control group treated with maprotiline (Map). The efficacy of treatment was evaluated before treatment and 14, 28 and 42 days after treatment, with Hamilton depression rating scale (HAMD), self-rating scale for depression (SDS), self-rating scale for anxiety (SAS) and clinical global impression (CGI), the adverse reaction was assessed by Asberg Rating Scale (ARS).</p><p><b>RESULTS</b>JYP was effective in treating depression, the markedly effective rate being 78.8%, corresponded to that of Map (82.8%, P > 0.05). After treatment, the scores assessed by HAMD, SDS and SAS were all lower than those before treatment (P < 0.01) respectively, but comparison between the two groups showed insignificant difference (P > 0.05). However, scores of ARS were significantly lower in the treated group than that in the control group, and the efficacy index of JYP was significantly higher than that of Map (P < 0.01).</p><p><b>CONCLUSION</b>JYP in treating depression shows the efficacy corresponded to that of Map and with less adverse reaction.</p>

Comparative study of electro-acupuncture and maprotiline in treating depression / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To compare the effect of electro-acupuncture (EA) and maprotiline (Map) in treating depression.</p><p><b>METHODS</b>Thirty patients of depression were treated with EA and 31 patients with Map orally taken respectively. The therapeutic effect and side-effect were evaluated by measurement of Hamilton Depression Rating Scale (HAMD), Self-Rating Scale for Depression (SDS), Self-Rating Scale for Anxiety (SAS), Clinical Global Impression Scale (CGI) and Asberg Rating Scale for side-effects (ARS) before treatment and on the day 14, 28 and 42 of the therapeutic course.</p><p><b>RESULTS</b>After treatment, the scores of HAMD and SDS lowered significantly (P < 0.01) than before treatment, and with insignificant difference between the group (P > 0.05). For patients with somatic syndrome, the HAMD score decrease rate was obviously higher in the Map group than that in the EA group. However, for the patients with anxiety somatization syndrome, the score of SAS, ARS in the EA group were significantly lower than those in the Map group (P < 0.05). Moreover, the efficacy index was higher in the EA group (P < 0.01).</p><p><b>CONCLUSION</b>Both EA and Map are effective in treating depression.</p>

Antidepressivos / Antidepressants

Os medicamentos antidepressivos tornaram a depressäo um problema médico com elevado potencial tratavel. Nas últimas décadas houve um grande avanço na pesquisa e novos compostos surgiram. Os antidepressivos de primeira geraçäo tiveram seu uso limitado devido a tolerabilidade e toxicidade. Os novos compostos, embora mais seguros, näo se mostraram superiores aos antidepressivos tradicionais. Neste artigo o autor revisa a farmacologia e as indicaçöes dos antidepressivos, assim como as indicaçöes e a eficácia diferencial entre os compostos clássicos e de nova geraçäo(au)

Estudio retrospectivo de veintidos años de uso clínico de maprotilina / Retrospective study of a twenty years of clinical use of maprotiline

El autor hace un estudio retrospectivo de múltiples casos de depresión tratados con maprotilina (ludiomil). Utiliza la clasificación nosológica de Paul Kielholz y hace un estudio sobre dicho medicamento

Tratamento ambulatorial de depressöes resistentes: infusöes venosas de antidepressivos / Ambulatory treatment of resistant depression by venous infusions of antidepressive agents

Infusöes venosas de antidepressivos é utilizada como técnica de tratamento de Depressöes resistentes, em regime ambulatorial. Em estudo aberto com 33 pacientes, procura-se verificar a eficácia e tolerância do tratamento com infusöes. Duas substâncias, clomipramina (preferentemente serotoninérgica) e Maprotilina (noradrenérgica), säo utilizadas no estudo. Modificaçäo da técnica usual, com aumento do tempo de perfusäo, e cuidados clínicos, possibilitam a aplicaçäo em regime extra-hospitalar. Os resultados indicam evoluçäo favorável em mais de 80 por cento dos casos, com baixo nível de efeitos colaterais. Seguimento de um ano é considerado.

double blind placebo controlled study comparing the CNS and antimuscarinic side effect of amitriptyline and maprotiline

A double blind placebo controlled cross over study randomized in a latin square design was conducted at Pharmacology Department of Rawalpindi Medical College on twelve healthy human volunteers of either sex, with ages between 20-25 years and a body weight between 50-60 kg to compare the C.N.S. and antimuscarinic side effects of tricyclic [Amitryptyline] and tetracyclic [Maprotiline] antidepressants Results revealed that amitriptyline causes more sedation than maprotiline. The antimuscarinic effects like dryness of mouth, decrease in salivary volume and impairment of visual accommodation are also more prominent with amitriptyline compared with maprotiline

Effects of maprotiline, nomifensine and Trazodone on gamma amino butyric acid turnover in the limbic system

The effects of chronic treatment with 3 antidepressant drugs: Maprotilline, Nomifensine and Trazodone on the turnover rate of gamma amino butyric acid were studied in 4 rat brain areas related to the limbic system. Trazodone markedly increased the Gamma amino butyric acid level in the hypothalamus and hippocampus but lowered its level in the amygdala and olfactory tubercle. Nomifesine increased its level in the hypothalamus and hippocampus and markedly decreased it in the olfactory tubercle. Maprotilline on the other hand consistently lowered its level in all 4 areas. These results indicate the involvement of gamma amino butyric acid in the mechanism of action of antidepressant drugs. Its possible role in modulating other neurotransmltters and production of antidepressant manifestations are discussed

Dosagem plasmática e metabolismo dos antidepressivos tricíclicos / Plasma measurement and metabolism of tricyclic antidepressant drugs

Neste artigo é exposto sucintamente aspectos do metabolismo dos antidepressivos tricíclicos (desmetilaçao e hipdroxilaçao) que devem ser levados em conta na interpretaçao das dosagens plasmáticas e efeitos clínicos destes medicamentos

Tratamento dos estados depressivos com associaçäo de clorimipramina e maprotilina em infusäo venosa gota a gota / Treatment of depressive states with association of clomipramine and maprotiline intravenous drip infusion

Os autores apresentam inicialmente uma revisäo bibliográfica do uso de infusäo endovenosa em psicofarmacoterapia, como também as principais teorias neuroquímicas das depressöes de fundamento biológico

Enfermedad de Chagas y transfusión sanguinea: actividad tripanocida del clorhidrato de maprotilina y del violeta de genciana / Chagas' disease and blood transfusion: trypanocidal activity of maprotiline hydrochloride and gentian violet

Se evaluó por inoculación en ratón la actividad tripanocida del Clorhidrati de Maprotilina comparativamente con la presentada por el Violeta de Genciana cuando estos compuestos se adicionaron a muestras de sangre conteniendo bajas concentraciones de parásitos. Ambas drogas presentaon actividad tripanocida cuando se las utilizó en concentraciónes del orden 10**-3M. Sin embargo, aun empleando esta concentración pudo detectarse esporádicamente infección en alguno de los animales inyectados con muestras de sangre conteniendo 10 o 100 tripomastigotes, despues de haber sido incubadas 24 h a 4-C con uno de ambos compuestos. Debido a la baja solubilidad del Clorhidrato de Maprotilina el presente estudio se realizó con muestras de sangre diluidas al medio siendo imposible evitar esta condición para la concentración 10**-3M de este compuesto. Estos resultados descartan el uso de clorhidrato de Maprotilina en bancos de sangre y previenen sobre la posibilidad eventual de transmitir infección por Trypanosoma cruzi aun con sangre tratada con Violeta de Genciana. De los 3 métodos utilizados para evaluar viabilidad parasitaria remanente en las muestras de sangre químicamente tratadas, el microhematocrito fue el más sensible

Tratamiento de la depresión con maprotilina en dosis única: un estudio abierto / Treatment of depresion with single doses of maprotiline: an open study

El presente ensayo, consistió en un estudio abierto, no comparativo de los efectos clínicos de 75 mgrs. de Maprotilina, en pacientes con Depresión Neurótica y en Reacciones Depresivas de Adaptación, cuya intensidad no hacía necesaria la hospitalización. El control de los pacientes, se realizó en la Consulta Externa del Servicio de Psiquiatría del Hospital Vargas de Caracas. Los autores evaluaron a los pacientes semanalmente, a partir del inicio del tratamiento. Para cuantificar los cambios ocurridos, se utilizó la Escola de Hamilton para depresión y un protocolo que contiene datos relativos a la evolución clínica, tratamientos previos, exploraciones cardiovasculares y de laboratorio, datos biográficos y escalas de evaluación para el médico y el paciente, que incluye el control de efectos colaterales atribuibles al medicamento. Al final del ensayo, casi las tres cuartas partes de la muestra presentó mejoría marcada en tanto que los restantes lo hicieron levemente. Se presentaron efectos secundarios leves en seis pacientes, que desaparecieron después de la segunda semana de tratamiento