A 80426

A 80426 is an orally active serotonin (5-HT uptake) inhibitor (IC₅₀ = 13 nM; K_i = 3.8 nM) and α₂-Adrenoceptor receptor antagonist (K_i = 2 nM). A 80426 shows weak antagonistic effect to dopamine D₁ receptor (K_i = 744 nM) and D₂ receptor (K_i = 52 nM). A 80426 upregulates the expression and activity of TRPV1, activates the NF-κB and PI3K pathways, and reduces the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. A 80426 can be used in research related to inflammatory pain and depression^[1][2]. In Vitro:A 80426 potently binds to serotonin uptake sites (K_i = 3.8 nM) and α₂-adrenoceptors (K_i = 2.0 nM), and weakly binds to dopamine D₁ (K_i = 744 nM) and D₂ (K_i = 52 nM) receptors in cell-free radioligand binding assays^[2]. In Vivo:A 80426 (10 mg/kg; i.p.; once daily for 2 consecutive days) exerts analgesic and anti-inflammatory effects in the CFA (HY-153808)-induced inflammatory pain model of C57BL/6 mice^[1].
A 80426 (10 mg/kg; i.p.; once daily; for 2 consecutive days) exerts no analgesic or anti-inflammatory effects in the CFA-induced inflammatory pain model of TRPV1^-/- mice, confirming that its activity is dependent on TRPV1^[1].
A 80426 (0.3-30 μmol/kg; p.o.; single dose; 0.3-10 μmol/kg; p.o.; once daily; for 14 consecutive days) blocks serotonin-mediated PCA-induced hyperactivity in rats, with subchronic administration (ED₅₀ = 4.1 μmol/kg) being more potent than acute oral administration (ED₅₀ = 13 μmol/kg); at oral doses of 6.7 and 22 μmol/kg, the pharmacodynamic effect lasts up to 12 hours^[2].
A 80426 (6.7-224 μmoles/kg; i.p.; single administration) does not block Clonidine (HY-12721)-induced hypothermia or reduced locomotor activity in mice when administered i.p. at doses up to 224 μmol/kg, but enhances clonidine-induced hypothermia at i.p. doses of 6.7, 22 and 67 μmol/kg^[2].
A 80426 (60-300 μmol/kg; p.o.; single administration) acts as a weak in vivo α₂-adrenergic receptor antagonist in rats. An oral dose of 300 μmol/kg is required to produce a mydriatic response shift similar to that induced by an oral dose of 100 μmol/kg Rauwolscine (HY-12710), and its pK_B value is 4.40^[2].
A 80426 (0.3-30 μmol/kg; p.o.; single administration; 2.2-6.7 μmol/kg; p.o.; once daily; for 5 consecutive days) reverses passive avoidance deficits in olfactory bulbectomized rats, with an acute ED₇₀ of 7.1 μmol/kg for oral administration, and remains effective after once-daily oral administration at doses of 2.2 and 6.7 μmol/kg for 5 consecutive days^[2].
A 80426 (6.7-22 μmol/kg; i.p.; single administration; 22 μmol/kg; i.p.; once daily for 3 consecutive days) dose-dependently reduces food intake after acute administration in obese Zucker rats; under the condition of 3 consecutive days of administration, it decreases 24-hour food intake by 15%-20%^[2].
A 80426 (100-300 μmol/kg; p.o.; single administration; 6.7-67 μmol/kg; i.v.; cumulative administration every 30 minutes) causes mild, dose-dependent hypotension and transient bradycardia in conscious normotensive rats at oral doses of 100 and 300 μmoles/kg, while only transient bradycardia without significant blood pressure changes occurs at intravenous doses up to 67 μmol/kg^[2].