The mGlu7 negative allosteric modulator ADX71743 increases wakefulness and reduces REM and NREM sleep in rats.
In freely moving rats, subcutaneous administration of ADX71743 (50, 100, or 150 mg/kg) increased wakefulness by up to 100% and reduced REM sleep by up to 100% and NREM sleep by up to 75% (all P < .05). The drug also delayed NREM and REM sleep onset by nearly 2-fold for 2 hours after dosing, without altering motor activity or body temperature.
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The mGlu7 negative allosteric modulator ADX71743 increases wakefulness and reduces REM and NREM sleep in rats. The current body of evidence comprises 1 study. EvidenceHub rates the overall confidence at 26/100 (low).
The Claim
The mGlu7 negative allosteric modulator ADX71743 increases wakefulness and reduces REM and NREM sleep in rats.
This conclusion is most relevant to: Freely moving rats (implanted with EEG/EMG electrodes, telemetry devices, or microdialysis probes)..
What the Research Shows
The conclusion draws on 1 linked study. Highlights from the cited literature:
- ▸Negative allosteric modulator of the metabotropic glutamate receptor 7 ADX71743 increases wakefulness, reduces sleep, and alters stress-induced changes in the brain neurotransmitter levels. (The international journal of neuropsychopharmacology, 2026) —
How It Works
The proposed biological pathway:
- ▸ADX71743 selectively inhibits mGlu7 receptor activity
- ▸Reduced mGlu7 signaling alters sleep-wake regulatory circuits
- ▸Increases wakefulness and suppresses REM and NREM sleep
- ▸Modulates stress-induced neurotransmitter changes (maintains higher vHipp GABA and 5-HT levels)
Who Might Benefit
Evidence fit by population:
- ▸Freely moving rats (implanted with EEG/EMG electrodes, telemetry devices, or microdialysis probes).
Recommended Dose
50, 100, or 150 mg/kg (subcutaneous); primary effects observed across all doses.
Limitations & Caveats
Important context when interpreting this evidence:
- ▸Animal model (rats) limits direct generalizability to humans
- ▸No assessment of long-term effects or potential tolerance with repeated dosing
Frequently Asked Questions
What is ADX71743?▼
ADX71743 is a selective negative allosteric modulator (NAM) of the metabotropic glutamate receptor 7 (mGlu7), used in this study to investigate its role in sleep-wake regulation and stress reactivity in rats.
How did ADX71743 affect sleep in rats?▼
ADX71743 increased wakefulness by up to 100% and reduced REM sleep by up to 100% and NREM sleep by up to 75%, with effects lasting for at least 2 hours after dosing.
Did ADX71743 affect neurotransmitter levels?▼
Basal neurotransmitter levels were unchanged, but ADX71743 attenuated stress-induced declines in GABA and 5-HT in the ventral hippocampus, maintaining higher levels compared to vehicle-treated controls.
Is ADX71743 a stimulant?▼
No, ADX71743 did not alter locomotor activity or body temperature, indicating it has no locomotor stimulant or sedative-like effects.
References
- 1.Kalinichev M, Gruner JA, Flik G, Heins M, Haddouk H, Royer-Urios I, Bate ST, Poli S, Lütjens R. “Negative allosteric modulator of the metabotropic glutamate receptor 7 ADX71743 increases wakefulness, reduces sleep, and alters stress-induced changes in the brain neurotransmitter levels..” The international journal of neuropsychopharmacology, 2026. PMID: 42113604 DOI: 10.1093/ijnp/pyag025