Chronic dosing with mirtazapine does not produce sedation in rats

Abstract

Objective: Sedation/somnolence are major side effects of pharmacotherapies for depression, and negatively affect long-term treatment compliance in depressed patients. Use of mirtazapine (MIR), an atypical antidepressant approved for the treatment of moderate to severe depression with comorbid anxiety disorders, is associated with significant sedation/somnolence, especially in short-term therapy. Nonetheless, studies with human subjects suggest that MIR-induced sedation is transient, especially when high and repeated doses are used. The purpose of this study was to explore the effects of acute and chronic administration of different doses of MIR on sedation in the rat. Methods: Assessment of sedation was carried out behaviorally using the rotarod, spontaneous locomotor activity, and fixed-bar tests. Results: A 15-mg/kg dose of MIR induced sedative effects for up to 60 minutes, whereas 30 mg/kg or more produced sedation within minutes and only in the first few days of administration. Conclusion: These results suggest that 30 mg/kg is a safe, well-tolerated dose of MIR which generates only temporary sedative effects.

Mirtazapine attenuates anxiety- and depression-like behaviors in rats during cocaine withdrawal

“…For this study, the optimal mirtazapine dose (30 mg/kg) was determined in accordance with previous reports. They showed that ⩾30 mg/kg mirtazapine does not affect SLA (Salazar-Juárez et al, 2016) or produce sedation, nor does it induce weight gain (Bittolo et al, 2016; Salazar-Juárez et al, 2017), in rats.…”

Mirtazapine attenuates nicotine-seeking behavior in rats

“…Furthermore, we have previously reported that chronic dosing of 30 mg/kg of mirtazapine does not alter spontaneous locomotor activity (Salazar-Juárez et al, 2016) and/or cause sedation in rats and does not induce weight gain (Salazar-Juárez et al, 2017).…”

“…Graves and Napier (2011) found that mirtazapine decreases methamphetamine-seeking in rats. Other authors have shown that mirtazapine attenuates the expression of locomotor sensitization and place preference induced by methamphetamine, morphine, nicotine and cocaine (Barbosa-Méndez et al, 2017b,c;Graves et al, 2012b;Herrold et al, 2009;Salazar-Juárez et al, 2017;Voigt and Napier, 2012;Voigt et al, 2011).…”

Optimization of mirtazapine loaded into mesoporous silica nanostructures via Box-Behnken design: in-vitro characterization and in-vivo assessment

“…Group I received plain MRT after being suspended in water, group II was given MRT loaded into SBA-15 (optimized formula). Administration was orally by pharyngostomy tube (4 French) and dose equal to 15 mg/kg (El-Sisi et al., 2017 ; Salazar-Juárez et al., 2017 ). Orbital blood samples (0.5 ml) were collected at 0, 0.5, 1, 2, 3, 5, 8, 11, and 24 hours in a heparinized tube, centrifuged at 4000 rpm for 10 min to separate plasma.…”