ABSTRACT
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. .
Subject(s)
Animals , Male , Rats , Amitriptyline/pharmacology , Anti-Inflammatory Agents/pharmacology , Cell Degranulation/drug effects , Clomipramine/pharmacology , Maprotiline/pharmacology , Mast Cells/drug effects , Neutrophil Infiltration/drug effects , Carrageenan/adverse effects , Cell Movement/drug effects , Disease Models, Animal , Edema/chemically induced , Mast Cells/physiology , Rats, WistarABSTRACT
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
Subject(s)
Mice , Animals , Gentian Violet/pharmacology , Maprotiline/pharmacology , Trypanosoma cruzi/drug effects , Blood Transfusion/adverse effects , Chagas Disease/prevention & control , Trypanosoma cruzi/pathogenicitySubject(s)
Adult , Humans , Male , Female , Antidepressive Agents, Tricyclic/pharmacology , Salivation/drug effects , Parasympathetic Nervous System/drug effects , Sweating/drug effects , Amitriptyline/pharmacology , Clinical Trials as Topic , Double-Blind Method , Imipramine/pharmacology , Maprotiline/pharmacology , Mianserin/pharmacologyABSTRACT
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.