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 mg/0.1 mL/paw) or dextran (500 mg/0.1 mL/paw). Then, edema formation was measured hourly. Neutrophil migration to carrageenan (500 mg/pouch) and Nformyl-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.

Immune cellular profile of bisphosphonate‐related osteonecrosis of the jaw

“…Hydrated tissue sections (4 μ m) were immersed in 0.1% toluidine blue solution (in 0.9% sodium chloride) per 60s for histochemical assessment (Gurgel et al , ) and mast cell counting using the same methodology (Shaker et al , ).…”

Chronic maladaptive pain in cats: A review of current and future drug treatment options

“…Amitriptyline is a tricyclic antidepressant (TCA) that exerts its effect by inhibiting reuptake of the neurotransmitters serotonin, norepinephrine, and to a lesser effect, dopamine (Moore et al, 2012). It has also been shown to inhibit H1 release from mast cells in vitro (Gurgel et al, 2013). While its use in veterinary medicine has been limited primarily to behavioral disorders (Chew et al, 1998;Virga et al, 2001;Overall and Dunham, 2002), research in humans has demonstrated an analgesic effect in those suffering from interstitial cystitis (a urinary bladder disease with a chronic, neurogenic pain component; Hanno et al, 1989), and the drug is commonly used to treat neuropathic pain (Moore et al, 2012).…”

Depression in the Context of Medical Disorders: New Pharmacological Pathways Revisited

“…amitriptyline, clomipramine and maprotiline have an important anti-inflammatory role, which is dependent on the modulation of neutrophil migration and mast cell stabilization [109]. A shift in the balance of the inflammation toward an anti-inflammatory state in the hypothalamus i.e.…”

“…Unexpectedly, sertraline and docosahexaenoic acid had pro-inflammatory effects, with sertraline increasing interferon alpha and interleukin-6 and docosahexaenoic acid increasing interleukin-15, interleukin-1RA, interferon alpha, and interleukin-6, though these changes were also associated with a decrease in nuclear factor kB activity, suggesting distinct modes of action. Agomelatine and moclobemide had no effect on interleukin-6 secretion [109]. …”