tuneTypical Dose
900 mg three times daily (exploratory trial-based)
Chemical Compound
Ampalex
1-(quinoxalin-6-ylcarbonyl)piperidine
Evidence TierDWADA NOT PROHIBITED
watchEffect Window
Short to mid term in published studies. Durable benefit not established.
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
Ampalex (CX-516) is an investigational ampakine that modulates AMPA receptors, but controlled human trials did not show reliable cognitive benefit.
Early pilot work suggested possible attention and memory signals through AMPA-receptor potentiation, which is why the compound was studied in schizophrenia and fragile X syndrome. But the larger controlled trials were negative, and the overall record now looks more like a mechanistically interesting first-generation ampakine that failed to translate than a neglected cognitive enhancer.
AMPA receptor positive allosteric modulation with preclinical memory/circuit evidence. Human efficacy signals are inconsistent and unconfirmed in larger controlled trials.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- AMPA-mediated cognitive/learning endpoints in preclinical and early clinical research.
Secondary Outcomes
- Attention/memory exploratory outcomes in early schizophrenia studies.
Safety
Contraindications and Interactions
Contraindications
- Pregnancy
- Lactation
- Active neutropenia
- Uncontrolled psychiatric instability
- Severe hepatic or renal disease
Side effects
- Headache
- Nausea
- Drowsiness
Interactions
- Myelosuppressive agents
- Hepatotoxic agents
- Overlapping CNS stimulatory stacks
Avoid if
- History of agranulocytosis
- Active malignancy
- Unstable liver disease
Evidence
Study-level References
ampalex-SRC-001Mechanistic review/clinical context review of AMPA potentiators
Sourceopen_in_newPubMed PMID: 15180479, DOI: 10.2174/1568007043337508
Population: Preclinical and clinical context summary
Dose protocol: Not primary for dose
Key findings: AMPA potentiation, potential therapeutic targeting of cognitive deficits, and neuroplasticity relevance.
Notes: Mechanism-only evidence. Does not establish clinical efficacy for Ampalex at population level.
Paper content
AMPA potentiation, potential therapeutic targeting of cognitive deficits, and neuroplasticity relevance.
ampalex-SRC-002Randomized placebo-controlled add-on trial
Sourceopen_in_newPubMed PMID: 17487227, DOI: 10.1038/sj.npp.1301444
Population: Adults with schizophrenia (clozapine, olanzapine, risperidone strata)
Dose protocol: 900 mg CX-516 three times daily, 4 weeks
Key findings: No significant difference from placebo on cognitive composite. Placebo improved more on PANSS total.
Notes: Most rigorous human signal in current record. Effect direction neutral.
Paper content
No significant difference from placebo on cognitive composite; placebo improved more on PANSS total.
ampalex-SRC-003Preliminary pilot randomized trial
Sourceopen_in_newPubMed PMID: 11593073, DOI: 10.1097/00004714-200110000-00005
Population: Adults with schizophrenia on clozapine
Dose protocol: Small dose-finding and fixed-dose trial structure
Key findings: Moderate-to-large effect sizes for attention/memory in pilot conditions. Sample size was small.
Notes: Exploratory signal, not practice- or guideline-level evidence.
Paper content
Moderate-to-large effect sizes for attention/memory in pilot conditions; sample size was small.
ampalex-SRC-004Case-series/randomized comparative early-phase study
Sourceopen_in_newPubMed PMID: 12223253, DOI: 10.1016/S0920-9964(01)00311-5
Population: Partially refractory schizophrenia cohort
Dose protocol: Escalation to 900 mg three times daily
Key findings: Limited benefit signal. Transient leukopenia and transient hepatic enzyme elevation noted.
Notes: Small sample, mixed intent, limited generalizability.
Paper content
Limited benefit signal; transient leukopenia and transient hepatic enzyme elevation noted.
ampalex-SRC-005Preclinical repeated-dose rodent behavior/electrophysiology
Sourceopen_in_newPubMed PMID: 9502832, DOI: 10.1523/JNEUROSCI.18-07-02748.1998
Population: Rats in delayed-nonmatch-to-sample memory tasks
Dose protocol: Repeated CX-516 dosing
Key findings: Improved spatial delayed-memory behavior and hippocampal firing measures.
Notes: Strong mechanistic signal with preclinical translatability uncertainty.
Paper content
Improved spatial delayed-memory behavior and hippocampal firing measures.
ampalex-SRC-006Structural pharmacology
Sourceopen_in_newPubMed PMID: 23999288, DOI: 10.1107/S0907444913011839
Population: In vitro AMPA ligand-binding structure
Dose protocol: N/A
Key findings: CX-516 structural fit is consistent with AMPA positive allosteric modulation.
Notes: Not a clinical effectiveness source.
Paper content
CX-516 structural fit is consistent with AMPA positive allosteric modulation.
ampalex-SRC-007Phase II randomized double-blind placebo-controlled trial
Sourceopen_in_newBerry-Kravis E, et al. "Effect of CX516, an AMPA-modulating compound, on cognition and behavior in fragile X syndrome: a controlled trial." J Child Adolesc Psychopharmacol. 2006;16(5):525-540. PMID: 17069542. DOI: 10.1089/cap.2006.16.525.
Population: Participants with fragile X syndrome
Dose protocol: 4-week randomized placebo-controlled trial in fragile X syndrome
Key findings: No significant improvement on the primary memory endpoint or secondary language, attention, behavior, or functioning measures versus placebo.
Notes: Negative efficacy signal in a second human population, reinforcing that early pilot promise did not replicate.
Paper content
This controlled fragile X trial is important because it tested CX516 in a second human population after the early schizophrenia pilot work. The result was negative across the primary memory endpoint and across secondary measures of language, attention, behavior, and global functioning.
The paper does not prove that all AMPA-positive allosteric modulation strategies fail, but it does strengthen the conclusion that first-generation CX516 did not translate into clinically meaningful cognitive benefit despite plausible mechanism and tolerable short-term safety.