Amitriptyline and acute inflammation: a study using intravital microscopy and the carrageenan-induced paw edema model.
OBJECTIVE
Antidepressants are reported to exhibit antiinflammatory effects. However, mechanisms involved in this action have not been elucidated. Thus, the objectives of the present study were (a) to evaluate the effects of amitriptyline on the acute inflammatory process, and (b) to investigate the participation of α(1)-adrenergic receptors and glucocorticoids as possible mechanisms implicated in the amitriptyline action on inflammation.


RESULTS
Single and multiple doses of amitriptyline were administered to rats submitted to the carrageenan-induced paw edema model. The results showed a significant antiedematous reaction to amitriptyline, mainly when administered at each elimination half-life. The next step was to evaluate its effects on leukocyte behavior, using intravital microscopy. Amitriptyline produced a significant effect on leukocyte behavior. To investigate possible mechanisms involved, a glucocorticoid receptor antagonist (RU-486) and an α(1)-adrenergic receptor antagonist (prazosin) were used. RU-486 administration lacked the ability to decrease the amitriptyline antiinflammatory effects in the carrageenan-induced paw edema model. Prazosin pretreatment potentiated the amitriptyline antiinflammatory effect without presenting an effect per se.


CONCLUSIONS
The present study shows the ability of amitriptyline to decrease edema and affect leukocyte behavior in an acute inflammatory process; and, for the first time to our knowledge, we suggest the involvement of α(1)-adrenoceptors in the antiinflammatory effects of amitriptyline.
Vismari
L
L
Neuroimmunomodulation Research Group, Department of Pathology, São Paulo University, São Paulo, Brazil.
Alves
G J
GJ
Palermo-Neto
J
J
D000639:Amitriptyline / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002351:Carrageenan; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy / Q000503:physiopathology; D006207:Half-Life; D007249:Inflammation / Q000188:drug therapy* / Q000503:physiopathology; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008853:Microscopy / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D018340:Receptors, Adrenergic, alpha-1; D011965:Receptors, Glucocorticoid; D000639:Amitriptyline; D002351:Carrageenan