AVL‑3288
α7 nicotinic receptor type-I positive allosteric modulator that reached human Phase 1.
Pharmacology
Contents
WHAT IS AVL-3288?
Detailed overview
AVL-3288 (also known as UCI-4083 or XY-4083) is a type I positive allosteric modulator (PAM) of the α7 nicotinic acetylcholine receptor investigated as a cognitive enhancer. It does not activate the receptor directly but strengthens the receptor's response to the brain's own acetylcholine: as a type I modulator it mainly enhances the peak current while largely preserving the receptor's rapid desensitization. In rodent models it improved cognition, reduced autism-like behaviors, and rescued learning and memory deficits associated with traumatic brain injury. In humans it reached Phase 1, where it was safe and well tolerated with an early neurocognitive signal; however, in a randomized trial in schizophrenia patients it showed no efficacy compared with placebo. It is currently not an approved medicine or marketed supplement and remains investigational.
Mechanism
α7 nAChR type-I PAM
Evidence
Human Phase 1 + schizophrenia RCT (efficacy negative)
Legal status
Investigational, not approved
Receptor profile
- α7 nicotinic acetylcholine receptorsStrong
- Acetylcholine signalingModerate
- Type-I PAM (preserves desensitization)Moderate
Safety
Side effects, stop signs, contraindications
Side effects · 4
- In Phase 1 human trials it was safe and well tolerated, with no reported safety concerns
- Theoretical symptoms of cholinergic overstimulation (nausea, headache, dizziness) typical of the class
- In a randomized trial in schizophrenia patients it showed no cognitive benefit over placebo
- Limited number of human trials: long-term safety in humans is not fully characterized
Contraindications · 3
- Pregnancy and breastfeeding: safety not established, avoid
- Unapproved, investigational compound; not recommended outside clinical supervision
- Caution with other cholinergic agents (cholinesterase inhibitors, nicotinic agonists) due to additive effects
Related Nootropics
Same therapeutic category
Studies
Related research and clinical findings
First in human trial of a type I positive allosteric modulator of alpha7-nicotinic acetylcholine receptors: Pharmacokinetics, safety, and evidence for neurocognitive effect of AVL-3288
Gee KW, Olincy A, Kanner R, et al.
Double blind, two dose, randomized, placebo-controlled, cross-over clinical trial of the positive allosteric modulator at the alpha7 nicotinic cholinergic receptor AVL-3288 in schizophrenia patients
Kantrowitz JT, Javitt DC, Freedman R, et al.
Positive allosteric modulation of the α7 nicotinic acetylcholine receptor as a treatment for cognitive deficits after traumatic brain injury
Titus DJ, Johnstone T, Johnson NH, et al.
Enhancing cognitive function in chronic TBI: The Role of α7 nicotinic acetylcholine receptor modulation
Sangadi DK, Titus DJ, Johnson NH, et al.
Chronic administration of caffeine, modafinil, AVL-3288 and CX516 induces time-dependent complex effects on cognition and mood in an animal model of sleep deprivation
Güvel MC, et al.
Allosteric modulation of nicotinic and GABA(A) receptor subtypes differentially modify autism-like behaviors in the BTBR mouse model
Yoshimura RF, Hogenkamp DJ, Li WY, et al.
FAQ
FAQ
α7 nicotinic receptor type-I positive allosteric modulator that reached human Phase 1.
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Structure & chemistry
The information here is strictly for educational and scientific purposes. It does not replace medical advice or clinical consultation, and it does not encourage illegal substance or pharmaceutical use. Data is sourced. When in doubt, consult your doctor.