Efeitos farmacológicos do composto 7 cloro-4-(fenilselanil) quinolina em modelos experimentais de fibromialgia em camundongos machos e fêmeas

Abstract

Fibromyalgia is a chronic syndrome characterized by widespread pain and associated comorbidities, such as depression. Current pharmacological treatments in clinical practice present limited efficacy and adverse effects, highlighting the need for new therapies. The compound 7-chloro-4-(phenylselanyl)quinoline (4-PSQ) emerges as a novel candidate, particularly due to its promising pharmacological properties linked to its multi-target mechanism of action. Thus, the present study evaluated the effects of 4-PSQ on pathophysiological mechanisms of fibromyalgia, including monoaminergic dysfunction, glutamatergic dysregulation, HPA axis dysfunction, oxidative stress, and electrolyte imbalances. For this purpose, two animal models were used: chemical induction with reserpine (0.5 mg/kg, subcutaneous) and environmental induction with intermittent cold stress (ICS), allowing for a comparison of treatment effects in male and female mice in both chemically and environmentally induced models of fibromyalgia. After model induction, the animals received 4-PSQ (1 mg/kg, intragastrically [i.g.]), duloxetine (30 mg/kg, i.g.; positive control), or vehicle (canola oil, 10 mL/kg). Behavioral testing was conducted thirty minutes later of treatment. The results indicate that 4-PSQ attenuated nociceptive and depressive behaviors in both models, similarly to DXT. Its effects were associated with modulation of serotonin and glutamate levels, normalization of MAO-A and ATPase activities, and regulation of oxidative stress in the central nervous system of mice, in a sex- and model-dependent manner. Furthermore, 4-PSQ attenuated HPA axis activation in female mice exposed to ICS. These findings suggest that 4-PSQ may serve as a promising foundation for the development of more effective therapies for fibromyalgia.