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. .

Comparing the effects of clomipramine and fluoxetine on fasting blood glucose in children with obsessive-compulsive disorder

This study was conducted to compare the effects of clomipramine and fluoxetine on fasting blood glucose [FBS] in children with obsessive-compulsive disorder [OCD]. Thirty nondiabetic children with OCD entered this randomized trial. Subjects were between 7 to 17 years of age and had not received any medication that could affect blood glucose level for at least 2 weeks prior to the initiation of the study. Patients were assigned to receive 20 to 60 mg/d of fluoxetine or 75 to 200 mg/d of clompiramine for 8 weeks. The exclusion criteria were pregnancy and lactation, history of diabetes mellitus, any liver and thyroid disorder, epilepsy and major heart disease. Additionally, none of the patients should have received electroconvulsive therapy within 6 months prior to the initiation of the study. FBS levels were measured at baseline, 4 and 8 weeks after the initiation of the trial. In the fluoxetine group, FBS level was decreased from 82.93 mg/dL [baseline] to 79.73 mg/dL at week 4 [P<0.001] and to 72.53 mg/dL at week 8 [P<0.001]. On the other hand, in the clomipramine group, FBS level was increased from 84.93 mg/dL [baseline] to 87.00 mg/dL at week 4 [P<0.05] and to 95.33 mg/dL at week 8 [P<0.001]. This 8-week study demonstrated that FBS levels may decrease in children with OCD who received flouxetine, and may increase in those treated with clomipramine. Therefore, it is suggested that FBS levels should be monitored and taken into consideration when choosing between fluoxetine and clomipramine in the treatment of OCD

Tamamho do efeito da clomipramina no transtorno obsessivo-compulsivo / The effect-size of clomipramine in obsessive-compulsive disorder

A clomipramina foi o primeiro medicamento a induzir efeitos terapêuticos específicos no transtorno obsessivo-compulsivo em estudos empíricos, abertos, em doses em torno de 200mg/dia, após três meses de tratamento. Estudos duplo-cegos, comparativos com o placebo e com outros medicamentos, confirmaram a eficácia da clomipramina. A clomopramina é eficaz no tratamento do TOC quando utilizada em doses elevadas (mais de 200 mg/dia) e por tempo adequado (mínimo de 10 semanas). O efeito antiobsessivo da clomipramina é independente da existência de depressäo e superior ao de outros medicamentos estudados em estudos controlados. O tamanho do efeito (TE) da clomipramina no TOC calculado como a proporçäo de respondedores ao placebo é maior do que os tamanhos dos efeitos (TEs) dos inibidores seletivos da recaptaçäo de serotonina (ISRSs)

Efeitos da moclobemida sobre os processos mnemônicos e de aprendizagem em ratos, em modelo de condicionamento operante / Effects of moclobemide on mnemonics and learning processes in an operative behavior of rats

A moclobemida, um antidepressivo inibidor reversível da MAO-A, foi utilizada num experimento em ratos no intuito de verificar se a droga provoca alguma alteração no comportamento discriminatório. Não foi encontrado na literatura nenhum experimento similar onde foram usados animais. No experimento foi utilizada a caixa de Skinner como meio de avaliação e observação do comportamento do animal. Os ratos foram treinados a associar o estímulo luminoso ao ato de beber água. No grupo controle, o índice discriminativo manteve-se praticamente constante (97 por cento), e no grupo tratado com moclobemida observou-se uma queda significativa de 97 por cento para 72 por cento ao final do experimento. Com resultados obtidos no experimento, concluímos que a moclobemida tem efeitos deletérios na memória dos animais de experimentação

Interaction between clonidine and clomipramine on analgesia and brain transmitters in different areas of mouse brain

The antinocieptive axctive of clonidine [30 micro g/Kg] I.P., clompiramine [650 micro g/Kg] I.P. and their combination was studied by the phenylquinone writhing test in mice all through 30 minutes. The effect of these drugs on the level of brain transmitters [noradrenaline. Serotonin and dopamine] was estimated in the different areas of the brain in mice [cerebral cortex, hypothalamus and thalamuns, midbrain, medulla, pones and cerebellum]. It was found that clonidine produced a 100% protection against abdominal stretch responses and it produced a significant decrease in the norepineohrine content of the cerebral cortex, thalamus and hypothalamus, [44% and 36%] respectively, with insignificant change in the 5HT and dopamine content in all areas. Clomipramine, produced a significant mean percent protection of 49% against the writhing episodes. It produced a significant increase in the norepinephrine content in the cerebral cortex and thalamus and hypothalamus by 34% and 47% respectively. Clomipramine also produced a significant increase in the 5HT content by 60% in the cerebral cortex, 45% in thalamus and hypothalamus and 48% in the midbrain with no significant change in the dopamine level. The administration of clomipramine with clonidine decreased the 100% protection to 7% against the writhing responses. Concerning the effect of the combination of clomipramine and clonidine on brain transmitters, it was found to produce a significant increase in norepinephrine in the cerebral cortex [30%] and thalamus and hypothalamus [40%] and significant increase in 5HT by 50% and 29% in cerebral cortex, thalamus and hypothalamus and midbrain respectively. No significant change in dopamine was observed. It could be councluded that although clonidine offers a promising analgesia yet its action is decreased in patients taking tricylic antidepressants due to their interaction on the brain transmitter

Obsesión-compulsión: algunas perspectivas en el diagnóstico y el tratamiento / Obsessive-compulsive disorder: some perspectives in diagnosis and treatment

Se presentan los problemas actuales relacionados con la historia, fenomenología, epidemiología, psicofarmacología y neurobiología del Trastorno Obsesivo-Compulsivo. Se enfatiza la relación del Trastorno Obsesivo-Compulsivo y el Síndrome de Gilles de la Tourette

Inhibition of chlorpromazine-induced catalepsy by the 5-HT-1A ligands pindolol and Buspirone in mice

Neuroleptcs such as chlorpromazine and haloperidol are capable of inducing catalepsy in rodents. Non-selective 5-hydroxytryptamine (5-HT) antagonists such as methysergide reduce the cataleptic effect of haloperidol. The present study was designed to evaluate the particpation of 5-HT-1A receptors in chlorpromazine-induced catalepsy in mice. Pundolol and buspirone, two putative 5-HT-1A receptor ligands, were used. Pretreatment with these drugs reduced the cataleptic effect of chlorpromazine. Clomipramine, a 5-HT neuronal uptake blocker, reversed the inhibitory effect of buspirone. Pretreatment with clomipramine alone caused a potentiation of neuroleptic-induced catalepsy. These results suggest that central 5-HT-1A receptors play an important role in neuroleptic-induced catalepsy in mice

Tratamento da desordem de pânico com clomipramina: estudo aberto de 22 casos / Treatment of panic disorder with clomipramine: an open study of 22 cases

O autor apresenta um estudo clínico-empírico de 22 casos de Desordem de Pânico tratados com clomipramina e acompanhados por um período de 4,1 meses (+ ou - 3,1). Foram investigados a distribuiçäo por sexo, sintomatologia, fatores precipitantes e agravantes, incidência de doenças psicossomáticas, exames complementares e história familiar. É concluído que Desordem de Pânico ainda é pouco conhecida no Brasil, o que impossibilita um diagnóstico precoce e, conseqüentemente, se iniciar um tratamento adequado para assim se evitar as diversas complicaçöes que podem eventualmente prejudicar em muito o funcionamento (pessoal, familiar, profissional e social) desses indivíduos. O quadro clínico dos pacientes estudados se assemelha àquele proposto pelo DSM-III, contudo, este último deve ser acrescido dos seguintes sintomas: despersonalizaçäo, sintomas gastrointestinais e visuais, hipertensäo arterial durante a crise, sonolência e sensaçäo de moleza nas pernas ou no corpo. Chama-se a atençäo para a possibilidade de um ritmo circadiano da sintomatologia e talvez de uma alternância psicossomática. A resposta à clomipramina foi considerada excelente, a droga foi bem tolerada na dose utilizada de 10 a 50mg/dia, média de 26,4mg (+ ou - 14,7). Recomenda-se começar o tratamento com uma dose baixa (5 a 10mg/dia) a fim de se evitar o risco de agravamento inicial das crises, e aumentar a dose progressivamente de acordo com a resposta clínica. Há um período de latência de cerca de duas semanas, antes de se obter um resultado satisfatório

Effect of drugs influencing central 5-hydroxytryptamine mechanisms on amantadine-induced stereotyped behaviour in the rat.

Pretreatment with L-tryptophan, a precursor of 5-HT, was found to decrease the intensity of stereotyped behaviour induced by amantadine, while methysergide, a 5-HT antagonist, was found to increase the intensity of amantadine-induced stereotypy. These results suggest that the intensity of amantadine-induced stereotypy depends on the balance between central dopamine and 5-HT systems and that the central 5-HT systems may have an opposing, tonic effect upon central dopamine systems involved in the mediation of stereotypy. In contrast to L-tryptophan, however, pretreatment with quipazine, a 5-HT agonist, and clomipramine, a selective 5-HT neuronal reuptake blocker, was found to potentiate the stereotyped behaviour induced by amantadine.

Experimental evaluation of the antidepressant and neuroleptic activity of maprotiline.

Maprotiline, a tetracyclic antidepressant drug, was evaluated for antidepressant and neuroleptic activity. In antidepressant tests, maprotiline antagonized reserpine-induced ptosis in rats but, unlike the tricyclic antidepressants, was found to antagonize methamphetamine stereotypy in rats, to decrease the intensity of L-dopa induced behavioural syndrome in pargyline-pretreated mice and to be ineffective in intensifying the 5-HTP induced behavioural syndrome. In neuroleptic tests, maprotiline was found to, antagonize apomorphine-induced cage climbing behaviour, induce catalepsy, inhibit the CAR and traction response, decrease the spontaneous motor activity and exploratory behaviour, and to potentiate the hypnotic effect of pentobarbitone. Our results indicate that maprotiline exhibits a profile of activity which resembles the neuroleptics and most probably exerts post-synaptic striatal DA receptor blocking activity.

Experimental evaluation of the possible neuroleptic activity of clomipramine.

Clomipramine, a new antidepressant, differs from imipramine by having chlorine in position 3 of the aromatic ring and in this respect resembles chlorpromazine. Clomipramine was therefore tested for neuroleptic activity. Clomipramine and imipramine were ineffective in inhibiting the traction response and pinna reflex in mice and in inducing catalepsy in rat. Compared to chlorpromazine they were less potent in blocking conditioned avoidance response and in decreasing spontaneous motor activity and exploratory behaviour. In contrast to chlorpromazine, clomipramine like imipramine was found to enhance methamphetamine-induced stereotyped behaviour. Thus clomipramine like imipramine possesses negligible neuroleptic activity.