ADX71441

ADX71441 is an orally active, blood-brain barrier penetrant positive allosteric modulator of GABA_B receptor. ADX71441 potentiates the activity of endogenous GABA at GABA_B receptor, with an EC₅₀ of 96 nM. ADX71441 functionally inhibits adenosine transporters and 5-HT_2B receptor. ADX71441 produces anxiolytic-like, analgesic, muscle relaxant, hypothermic and overactive bladder inhibitory effects, reduces acute locomotor activity levels, decreases voluntary intake of alcohol and saccharin, attenuates stress-induced neuronal activation, and exhibits anti-hyperalgesic activity^[1][2][3][4]. In Vitro:ADX71441 (10^-10 to 10^-3 M; 180 s) acts as a positive allosteric modulator of recombinant human GABA_B receptors in HEK293 cells, potentiating GABA-induced calcium mobilization with an EC₅₀ of 29 ± 9 nM, exhibiting no significant direct agonist activity, and binding reversibly to the receptor^[1].
ADX71441 (10⁻¹³ to 10⁻³ M; 30 min + 30 min) potentiates GABA-induced G-protein activation at endogenous rat cortical GABA_B receptors with an EC₅₀ of 53 ± 14 nM, enhancing both the potency and efficacy of GABA^[1].
ADX71441 (10^-13 to 10^-3 M; 30 min + 30 min) potentiates GABA-induced G-protein activation at endogenous human cortical GABAB receptors with an EC₅₀ of 40 ± 7 nM, significantly enhancing GABA's potency and efficacy^[1].
ADX71441 (10 μM, up to 30 μM) is highly selective for GABAB receptors, with no activity on mGlu receptors and only weak off-target activity at the 5-HT2B receptor (IC₅₀ 6.06 μM) and adenosine transporter (IC₅₀ 0.24 μM)^[1]. In Vivo:ADX71441 (1-10 mg/kg; p.o.; single administration) produces a dose-dependent anxiolytic-like effect in the mouse pellet-burying test, with the minimum effective dose of 3 mg/kg^[1].
ADX71441 (1-10 mg/kg; p.o.; single administration) produces dose-dependent anxiolytic-like effects in the mouse elevated plus-maze test, with a minimum effective dose of 3 mg/kg^[1].
ADX71441 (0.3-3 mg/kg; p.o.; single administration) produces a dose-dependent anxiolytic-like effect in the elevated plus-maze test in rats, with the minimum effective dose being 3 mg/kg^[1].
ADX71441 (30 mg/kg; p.o.; single administration) exhibits anxiolytic-like effects in the elevated plus-maze test in rats, and such effects remain detectable 24 hours after administration^[1].
ADX71441 (1-10 mg/kg; p.o.; single administration) produces dose-dependent and time-dependent analgesic effects in the acetic acid-induced writhing test in mice^[1].
ADX71441 (10 mg/kg; p.o.; single administration) induces muscle relaxation in the rat rotarod test^[1].
ADX71441 (10 mg/kg; p.o.; single administration) reduces spontaneous locomotor activity in mice treated with acute intragastric administration^[1].
After acute oral administration, ADX71441 (3-30 mg/kg; p.o.; single dose) produces a dose-dependent reduction in spontaneous locomotor activity in rats, with a minimum effective dose of 3 mg/kg^[1].
Subchronic oral administration of ADX71441 (30 mg/kg; p.o.; once daily for 7 consecutive days) induces tolerance to its motor-suppressant effect in mice^[1].
ADX71441 (3-30 mg/kg; p.o.; single administration) exerts a dose-dependent hypothermic effect in mice via activation of GABAB receptors, with its minimum effective dose being 10 mg/kg^[1].
ADX71441 (3-30 mg/kg; p.o.; single administration) produces a dose-dependent, transient hypothermic effect in rats, with the minimum effective dose being 3 mg/kg^[1].
ADX71441 (1-10 mg/kg; p.o.; single administration) dose-dependently reduces the total number of micturition episodes, total urine volume, and average urine volume, and prolongs the first micturition latency in mice with furosemide (HY-B0135)-induced overactive bladder (OAB)^[2].
ADX71441 (1-3 mg/kg; i.v.; single administration) rapidly improves the urodynamic parameters of acetic acid (HY-Y0319)-induced overactive bladder (OAB) in guinea pigs^[2].
ADX71441 (1-30 mg/kg; i.p.; single administration) dose-dependently reduces 20% voluntary alcohol intake in non-addicted male Wistar rats^[3].
ADX71441 (1-3 mg/kg; i.p.; single administration) exhibits greater efficacy in reducing alcohol self-administration behavior in alcohol-dependent male Wistar rats^[3].
ADX71441 (3-10 mg/kg; i.p.; single administration) potently blocks cue-induced and stress-induced alcohol relapse-like drinking behavior in male Wistar rats trained to voluntarily consume alcohol^[3].
ADX71441 (3 mg/kg; i.p.; single administration) attenuates stress-induced neuronal activation within the brain region network (nucleus accumbens shell, central amygdala, dorsal raphe nucleus, and medial prefrontal cortex) associated with stress-induced relapse-like alcohol-seeking behavior in male Wistar rats^[3].
ADX71441 (0.3-15 mg/kg; p.o.; once daily for 7 consecutive days) exhibits dose-dependent anti-allodynic efficacy in a rat osteoarthritis model induced by Sodium iodoacetate (HY-D0849)^[4].
ADX71441 (1-10 mg/kg; p.o.; single administration) exerts muscle relaxant effects in rats^[4].