title: Amitriptyline, clomipramine, and maprotiline attenuate the inflammatory response by inhibiting neutrophil migration and mast cell degranulation.
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.
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Universidade Federal do Ceará (UFC), FortalezaCE, Brazil.
authors.forename: José Alves
authors.initials: JA
authors.lastname: Gurgel
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Universidade Federal do Ceará (UFC), FortalezaCE, Brazil.
authors.forename: Roberto César Pereira
authors.initials: RC
authors.lastname: Lima-Júnior
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Universidade Federal do Ceará (UFC), FortalezaCE, Brazil.
authors.forename: Cristiano Oliveira
authors.initials: CO
authors.lastname: Rabelo
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Universidade Federal do Ceará (UFC), FortalezaCE, Brazil.
authors.forename: Breno Bezerra Gomes Pinho
authors.initials: BB
authors.lastname: Pessoa
authors.affiliation: Department of Morphology, School of Medicine, UFC, FortalezaCE, Brazil.
authors.forename: Gerly Anne Castro
authors.initials: GA
authors.lastname: Brito
authors.affiliation: Department of Physiology and Pharmacology, School of Medicine, Universidade Federal do Ceará (UFC), FortalezaCE, Brazil.
authors.forename: Ronaldo Albuquerque
authors.initials: RA
authors.lastname: Ribeiro
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002351:Carrageenan / Q000009:adverse effects; D015550:Cell Degranulation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002997:Clomipramine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced; D008297:Male; D008376:Maprotiline / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D020556:Neutrophil Infiltration / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D000639:Amitriptyline; D008376:Maprotiline; D002351:Carrageenan; D002997:Clomipramine