Table 2.
Summary of efficacy of A‐582941 in animal models of cognition
| Cognitive domain | Model | Species | Effective dose(s) (μmol/kg) | Efficacy/dose (μmol/kg) | A‐582941 plasma concentration | |
|---|---|---|---|---|---|---|
| ng/mL | nM | |||||
| Working memory | Delayed match‐to‐sample (DMTS) | Monkey | 0.003–0.100 | +++/0.01 | 5.9 | 21.0 |
| Short‐term recognition memory | Social recognition | Rat | 0.1–1.0 (acute) | +++/0.10 | 4.8 | 17.0 |
| 1.8 μg/kg/day (chronic) | +++/OMP | 3.1 | 11.0 | |||
| Memory consolidation | 24‐hr inhibitory avoidance | Mouse | 0.01–1.00 | +++/0.10 | 2.6 | 9.3 |
| Sensory gating | Auditory evoked potential | Mouse | 3.0–10.0 (acute) | ++/3.0 (repeated dosing) | 44.0 | 157.0 |
| Response inhibition/impulsivity | 5‐trial inhibitory avoidance | Spontaneously‐hypertensive rat pup | 0.1–1.0* | ++/1.0 | 48.0 | 171.0 |
+++, 70–100%; ++, 30–70%; +, <30%; 0, inactive; efficacy relative to positive control used in the respective experiments; OMP, administration s.c. via osmotic minipump; testing after 7 days.
*P= 0.06 at highest dose.