| 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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: |
C57Bl6/J (male, adult, 24-30g)[1] |
| Dosage: |
1 mg/kg; 3 mg/kg; 10 mg/kg |
| Administration: |
p.o.; single dose; 60 minutes pre-test |
| Result: |
Showed no effect at 1 mg/kg.
Produced a ~55% reduction in buried marbles at 3 mg/kg.
Fully suppressed burying behavior at 10 mg/kg.
Reached mean plasma concentrations of 144 ng/mL (1 mg/kg), 341 ng/mL (3 mg/kg), and 629 ng/mL (10 mg/kg) at end of experiment.\nShowed no effect at 1 mg/kg.
Produced ~2-fold increases in open arm entries at 3 mg/kg and 10 mg/kg.
Produced a ~2-fold increase in time spent on open arms at 3 mg/kg, and an almost 3-fold increase at 10 mg/kg.
Showed no effect on closed arm exploration.
Reached mean plasma concentrations of 168 ng/mL (1 mg/kg), 399 ng/mL (3 mg/kg), and 688 ng/mL (10 mg/kg) at end of experiment. |
| Animal Model: |
Sprague-Dawley (male, adult, 250-350g)[1] |
| Dosage: |
0.3 mg/kg; 1 mg/kg; 3 mg/kg |
| Administration: |
p.o.; single dose; 60 minutes pre-test |
| Result: |
Showed no effect at 0.3 mg/kg and 1 mg/kg.
Produced more than 3-fold increases in open arm entries and more than 4-fold increases in time spent on open arms at 3 mg/kg.
Showed no effect on closed arm exploration.
Reached mean plasma concentrations of 46 ng/mL (1 mg/kg), 171 ng/mL (3 mg/kg) at end of experiment. |
| Animal Model: |
Sprague-Dawley (male, adult, 250-350g)[1] |
| Dosage: |
1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg |
| Administration: |
p.o.; single dose; 24 hours pre-test |
| Result: |
Showed no effect at 1 mg/kg and 3 mg/kg.
Showed a trend toward reduced open arm entries at 10 mg/kg.
Produced almost 4-fold increases in open arm entries and almost 4-fold increases in time spent on open arms at 30 mg/kg.
Showed no effect on closed arm entries.
Reached mean brain concentrations of 40 ng/g (1 mg/kg), 107 ng/g (3 mg/kg), 427 ng/g (10 mg/kg), and 1014 ng/g (30 mg/kg); mean plasma concentrations of 11 ng/mL (1 mg/kg), 52 ng/mL (3 mg/kg), 321 ng/mL (10 mg/kg), and 898 ng/mL (30 mg/kg) at end of experiment. |
| Animal Model: |
C57Bl6/J (male, adult, 24-30g; separate cohort from SLAC, Shanghai, China)[1] |
| Dosage: |
1 mg/kg; 3 mg/kg; 10 mg/kg |
| Administration: |
p.o.; single dose; 70 minutes pre-test (dose-response); 1, 2, 4 hours pre-test (time-course) |
| Result: |
Showed no effect at 1 mg/kg in dose-response study.
Produced a 55% reduction in writhes at 3 mg/kg, and an almost 90% reduction at 10 mg/kg in dose-response study.
Produced an ~80% reduction in writhes at 1 hour post-treatment, ~60% reduction at 2 hours, and ~25% reduction (trend) at 4 hours with 10 mg/kg in time-course study.
Reached mean plasma concentrations of 562 ng/mL (1 hour), 566 ng/mL (2 hours), and 343 ng/mL (4 hours) in time-course study. |
| Animal Model: |
Sprague-Dawley (male, adult, 250-350g)[1] |
| Dosage: |
1 mg/kg; 3 mg/kg; 10 mg/kg |
| Administration: |
p.o.; single dose; measured at 60, 120, 180 minutes post-treatment |
| Result: |
Showed no effect at 1 mg/kg and 3 mg/kg across all time points.
Reduced time on rotarod by approximately 50% at all time points at 10 mg/kg. |
| Animal Model: |
C57Bl6/J (male, adult, 24-30g)[1] |
| Dosage: |
1 mg/kg; 3 mg/kg; 10 mg/kg |
| Administration: |
p.o.; single dose; 60 minutes pre-test; monitored for 60 minutes |
| Result: |
Showed no effect at 1 mg/kg and 3 mg/kg.
Produced a ~40% reduction in total distance travelled at 10 mg/kg. |
| Animal Model: |
Sprague-Dawley (male, adult, 250-350g)[1] |
| Dosage: |
1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg |
| Administration: |
p.o.; single dose; 60 minutes pre-test; monitored for 60 minutes |
| Result: |
Showed no effect at 1 mg/kg.
Produced an ~50% reduction in total distance travelled at 3 mg/kg, ~85% reduction at 10 mg/kg, and almost 100% reduction at 30 mg/kg. |
| Animal Model: |
C57Bl6/J (male, adult, 24-30g; cohort from Charles River Laboratories, Wilmington, MA)[1] |
| Dosage: |
10 mg/kg; 30 mg/kg |
| Administration: |
p.o.; once daily for 7 days plus acute dose on day 8; 60 minutes pre-test on day 8; monitored for 60 minutes |
| Result: |
Showed no reduction in locomotor activity (total distance travelled or rearing) with acute 30 mg/kg dose in mice with sub-chronic 30 mg/kg treatment history.
Produced an ~50% reduction in total distance travelled and ~90% reduction in rears with acute 30 mg/kg dose, and no effect with acute 10 mg/kg dose in vehicle-treated mice. |
| Animal Model: |
C57Bl6/J (male, adult, 24-30g; cohort from Janvier, Le Genest Saint Isle, France)[1] |
| Dosage: |
3 mg/kg; 10 mg/kg; 30 mg/kg |
| Administration: |
p.o.; single dose; measured at 1, 2, 4 hours post-treatment (acute); p.o. 30 mg/kg plus oral CGP63360 30 minutes later (target engagement) |
| Result: |
Showed no effect at 3 mg/kg in acute dose-response study.
Produced a 1.5°C reduction at 1 and 2 hours at 10 mg/kg, and a ~3°C reduction at 1 and 2 hours plus 1.77°C reduction at 4 hours at 30 mg/kg in acute dose-response study.
Had hypothermic effects dose-dependently reversed by CGP63360 in target engagement study; 3 mg/kg CGP63360 returned body temperature to normal at 2 and 4 hours post-ADX71441 treatment. |
| Animal Model: |
Sprague-Dawley (male, adult, 250-350g)[1] |
| Dosage: |
1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg |
| Administration: |
p.o.; single dose; measured at 1, 2, 4, 20 hours post-treatment |
| Result: |
Showed no effect at 1 mg/kg.
Produced 0.5-1.2°C reductions at 1, 2, and 4 hours at 3 mg/kg and 10 mg/kg.
Produced 1.4-1.8°C reductions at 1, 2, and 4 hours at 30 mg/kg.
Showed no effect at 20 hours post-treatment across all doses. |
| Animal Model: |
C57Bl6/J (adult male, 24-30 g, overhydrated with water and challenged with furosemide to induce bladder overactivity)[2] |
| Dosage: |
1 mg/kg; 3 mg/kg; 10 mg/kg |
| Administration: |
p.o.; single dose |
| Result: |
Produced a 70% reduction in total urinary events, a more than threefold increase in latency to the first urinary event, a 55% reduction in total urinary volume, and an approximately 65% reduction in average urinary volume compared to vehicle-treated mice at 10 mg/kg.
Normalized urinary parameters to levels not significantly different from intact untreated controls for number of urinary events, latency to first event, and average urinary volume at 3 mg/kg and 10 mg/kg.
Normalized total urinary volume to levels not significantly different from intact untreated controls at 10 mg/kg.
Achieved plasma concentrations of 101 ng/mL (1 mg/kg), 208 ng/mL (3 mg/kg), and 652 ng/mL (10 mg/kg), corresponding to unbound plasma concentration/EC50 ratios of 0.36, 0.74, and 2.31 respectively. |
| Animal Model: |
Dunkin Hartley (adult female, 290-370 g, OAB induced by intravesical infusion of 0.2% acetic acid)[2] |
| Dosage: |
1 mg/kg; 3 mg/kg |
| Administration: |
i.v.; single bolus dose |
| Result: |
Significantly increased intercontraction interval and bladder capacity at 1 mg/kg and 3 mg/kg 0-15 minutes post-administration.
Significantly reduced micturition frequency compared to vehicle at 1 mg/kg 0-15 minutes post-administration.
Significantly increased threshold pressure compared to vehicle at 3 mg/kg 0-15 minutes post-administration.
Completely inhibited the micturition reflex, inducing overflow incontinence, in 5 out of 10 animals at 3 mg/kg.
Achieved plasma concentrations of 67 ng/mL (1 mg/kg) and 195 ng/mL (3 mg/kg), corresponding to unbound plasma concentration/EC50 ratios of 0.3 and 0.9 respectively. |
| Animal Model: |
Wistar rats (adult male, 200-225g at study initiation, trained to self-administer 20% alcohol on FR2 schedule)[3] |
| Dosage: |
1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg |
| Administration: |
i.p. |
| Result: |
Showed no significant reduction in alcohol reinforcers earned or active lever presses, and no effect on locomotor activity at 1 mg/kg.
Produced statistically significant reduction in alcohol reinforcers earned and active lever presses , no alteration to locomotor activity, and potent reduction in alcohol breakpoints at 3 mg/kg.
Produced statistically significant reduction in alcohol reinforcers earned and active lever presses, no alteration to locomotor activity, and potent reduction in alcohol breakpoints at 10 mg/kg.
Produced statistically significant reduction in alcohol reinforcers earned and active lever presses, and significant reduction in locomotor activity at 30 mg/kg. |
| Animal Model: |
Wistar rats (adult male, 200-225g at study initiation; alcohol-dependent via chronic intermittent 14-hour daily alcohol vapor exposure for 8 weeks; non-dependent control exposed to normal air)[3] |
| Dosage: |
1 mg/kg; 3 mg/kg |
| Administration: |
i.p. |
| Result: |
Significantly decreased alcohol reinforcers earned and active lever presses in alcohol-dependent rats but had no significant effect in non-dependent rats at 1 mg/kg.
Significantly decreased alcohol reinforcers earned and active lever presses in both alcohol-dependent and non-dependent rats at 3 mg/kg. |
| Animal Model: |
Wistar rats (adult male, 200-225g at study initiation, trained to self-administer 20% alcohol, extinction trained for alcohol-seeking behavior)[3] |
| Dosage: |
3 mg/kg; 10 mg/kg |
| Administration: |
i.p. |
| Result: |
Potently blocked cue-induced relapse-like alcohol seeking and stress-induced relapse-like alcohol seeking at 3 mg/kg.
Potently blocked cue-induced relapse-like alcohol seeking and stress-induced relapse-like alcohol seeking at 10 mg/kg. |
| Animal Model: |
Wistar rats (adult male, 200-225g at study initiation, trained to self-administer 20% alcohol, extinction trained for alcohol-seeking behavior)[3] |
| Dosage: |
3 mg/kg |
| Administration: |
i.p. |
| Result: |
Significantly decreased c-Fos expression in the nucleus accumbens shell, central amygdala, and dorsal raphe nucleus compared to vehicle.
Showed a trend for reduced c-Fos expression in the medial prefrontal cortex.
Significantly suppressed activation of a stress-responsive brain network consisting of the dorsal raphe nucleus, nucleus accumbens shell, and medial prefrontal cortex, whose activity correlated strongly with stress-induced relapse-like behavior. |
| Animal Model: |
Sprague-Dawley rats (adult male, 250-350 g, monosodium iodoacetate-induced osteoarthritis)[4] |
| Dosage: |
0.3 mg/kg; 1 mg/kg; 3 mg/kg; 15 mg/kg |
| Administration: |
p.o.; once daily; 7 days |
| Result: |
Produced a 2-fold increase in ipsilateral joint compression threshold 2 hours post-administration, as well as 1.3-fold and 1.7-fold increases 1 and 4 hours post-administration, respectively, with 15 mg/kg acutely on post-MIA day 14.
Showed no significant acute efficacy on day 14 with 0.3, 1, 3 mg/kg.
Produced consistent 1.5-fold increases in joint compression threshold at all tested time points with 15 mg/kg on post-MIA day 21 after 7 days of daily treatment.
Produced statistically significant, modest increases in joint compression threshold, particularly at 2 and 4 hours post-dosing, with 1 mg/kg and 3 mg/kg on post-MIA day 21 after 7 days of daily treatment. |
| Animal Model: |
Sprague-Dawley rats (adult male, 250-350 g, rotarod-tested healthy)[4] |
| Dosage: |
1 mg/kg; 3 mg/kg; 10 mg/kg |
| Administration: |
p.o.; single dose |
| Result: |
Had no significant effect on time spent on the rotarod with 1 mg/kg and 3 mg/kg.
Produced an approximately 50% reduction in time spent on the rotarod 2 and 3 hours post-dosing compared with vehicle treatment with 10 mg/kg. |
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