The Benfotiamine Phase 2 trial (NCT06223360) represents a critical evaluation of a metabolic approach to Alzheimer's disease treatment. Unlike amyloid-targeting immunotherapies that dominate current AD drug development, benfotiamine takes a fundamentally different strategy: targeting the profound cerebral glucose hypometabolism that characterizes Alzheimer's disease pathology. This trial investigates whether improving brain energy metabolism can slow or modify disease progression in patients with early-stage Alzheimer's disease.
Benfotiamine is a synthetic derivative of thiamine (vitamin B1) that readily crosses the blood-brain barrier and activates thiamine-dependent metabolic pathways critical for neuronal energy production. The scientific rationale stems from decades of research demonstrating that cerebral glucose metabolism is significantly impaired in AD, with reductions detectable decades before clinical symptoms appear. This metabolic deficit affects the very pathways that benfotiamine is designed to support.
| Parameter |
Details |
| NCT Number |
NCT06223360 |
| Phase |
Phase 2 |
| Status |
ACTIVE_NOT_RECRUITING |
| Sponsor |
Alzheimer's Therapeutic Research Institute |
| Enrollment |
406 participants |
| Enrollment Type |
ACTUAL |
| Study Type |
INTERVENTIONAL |
| Start Date |
January 15, 2024 |
| Completion Date |
December 31, 2026 |
| Last Updated |
February 15, 2026 |
Benfotiamine serves as a pro-drug that increases thiamine levels in the brain and activates critical thiamine-dependent enzymes. Thiamine is an essential cofactor for three key enzyme complexes in cerebral energy metabolism:
-
Pyruvate Dehydrogenase Complex (PDHC)
- Catalyzes the conversion of pyruvate to acetyl-CoA
- Links glycolysis to the citric acid cycle (Krebs cycle)
- PDHC activity is reduced by 40-70% in AD brain tissue
- This reduction severely impairs the brain's ability to generate ATP from glucose
-
Alpha-Ketoglutarate Dehydrogenase (α-KGDH)
- Key rate-limiting enzyme in the citric acid cycle
- Highly vulnerable to oxidative damage in AD
- Activity correlates with cognitive function in AD patients
- Supports mitochondrial energy production and neurotransmitter synthesis
-
Transketolase (TK)
- Central enzyme in the pentose phosphate pathway
- Generates NADPH for antioxidant defense
- Supports lipid synthesis and cellular repair
- Activity is impaired in AD brain
The brain relies almost exclusively on glucose for energy, consuming approximately 20% of the body's glucose despite being only 2% of body weight. In Alzheimer's disease, this glucose metabolism is severely impaired:
Patterns of Hypometabolism:
- Posterior cingulate: Often the first region affected
- Temporal and parietal cortex: Progressive decline with disease
- Prefrontal cortex: Associated with executive dysfunction
- Hippocampus: Early involvement in memory impairment
Consequences of Hypometabolism**:
- Reduced ATP production compromises neuronal function
- Inability to maintain ion gradients disrupts neurotransmission
- Impaired cellular repair mechanisms accelerate neurodegeneration
- Vulnerable neurons are unable to withstand pathological insults
Beyond enzyme activation, benfotiamine provides additional benefits:
-
Advanced Glycation End Products (AGEs) Reduction
- AGEs form when glucose or its metabolites modify proteins
- AGE accumulation in AD brain contributes to:
- Chronic inflammation (RAGE receptor activation)
- Protein cross-linking and aggregation
- Mitochondrial dysfunction
- Benfotiamine inhibits AGE formation
-
Amyloid-Beta Toxicity Mitigation
- Energy-deprived neurons are more vulnerable to Aβ toxicity
- Improving metabolism protects against:
- Oxidative stress
- Calcium dysregulation
- Apoptotic pathways
-
Neuroinflammation Modulation
- Mitochondrial dysfunction triggers inflammatory responses
- Benfotiamine reduces:
- Microglial activation
- Pro-inflammatory cytokine production
- Oxidative stress
The thiamine hypothesis proposes that thiamine deficiency, either absolute or functional, contributes to the characteristic cerebral hypometabolism of Alzheimer's disease:
Evidence Supporting the Hypothesis:
- Post-Mortem Studies: AD brains show significantly reduced thiamine-dependent enzyme activities
- Imaging Studies: FDG-PET demonstrates cerebral hypometabolism decades before diagnosis
- Animal Models: Thiamine deficiency reproduces key AD pathological features
- Clinical Observations: AD patients often show signs of thiamine deficiency
Why Thiamine Supplementation Has Failed Previously:
- Thiamine itself has poor brain penetration
- Standard doses cannot overcome the magnitude of deficiency
- Short-term supplementation cannot reverse chronic deficits
- Benfotiamine's lipophilic nature overcomes these limitations
The benfotiamine trial represents a fundamentally different therapeutic approach:
| Aspect |
Amyloid-Targeted |
Metabolic Therapy |
| Target |
Amyloid plaques |
Brain energy metabolism |
| Mechanism |
Remove pathological protein |
Support cellular function |
| Rationale |
Remove upstream trigger |
Support downstream function |
| Stage in Disease |
Requires early intervention |
May work across stages |
| **Combination Potential |
Limited |
Excellent |
This approach may offer advantages:
- Works through endogenous cellular mechanisms
- Addresses multiple downstream consequences of Aβ
- May be effective even if amyloid removal is incomplete
- Compatible with combination therapy approaches
Extensive preclinical work supports benfotiamine development:
Animal Studies:
- Benfotiamine improves memory in APP/PS1 transgenic mice
- Reduces amyloid plaque burden by 30-50%
- Decreases neuroinflammation markers
- Preserves hippocampal neuron numbers
- Improves cerebral glucose metabolism on FDG-PET
Mechanistic Studies:
- Activates PDHC in brain tissue
- Increases ATP production in neurons
- Reduces AGE formation
- Decreases oxidative stress markers
The trial employs a randomized, double-blind, placebo-controlled design:
- Enrollment: 406 participants with early AD
- Randomization: 1:1 ratio to benfotiamine or placebo
- Duration: 52 weeks (1 year)
- Dosing: Oral benfotiamine twice daily
- Benfotiamine Arm: Active treatment with 300mg benfotiamine twice daily
- Placebo Arm: Matching placebo capsules
The Phase 2 design reflects learnings from earlier studies:
- Sufficient duration to detect metabolic effects
- Adequate sample size for signal detection
- Early-stage patients most likely to benefit
- Comprehensive biomarker program
The trial enrolls patients with early-stage Alzheimer's disease:
- Diagnosis: Probable AD per NIA-AA criteria
- Stage: Mild cognitive impairment due to AD or mild AD dementia
- Age: 50-85 years
- MMSE: 20-26 (mild impairment)
- Age 50-85 years
- Meet NIA-AA criteria for MCI due to AD or mild AD dementia
- MMSE score 20-26
- Confirmed amyloid pathology (PET or CSF)
- Stable on background AD medications (if applicable)
- Able to comply with study procedures
- Significant neurological disease other than AD
- Psychiatric conditions that could affect assessment
- Active cancer or life-threatening medical conditions
- Contraindications to study medication
- Previous thiamine supplementation (within 3 months)
- Significant renal or hepatic impairment
¶ Primary and Secondary Endpoints
Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
The ADAS-Cog is the gold standard for cognitive assessment in AD trials:
- 11-item version assesses:
- Word recall
- Naming
- Commands
- Construction
- Ideational praxis
- Orientation
- Word recognition
- Remembering instructions
- Higher scores indicate greater impairment
- Clinically meaningful change: 4-6 points
Safety and Tolerability
Comprehensive safety assessment:
- Adverse event monitoring
- Laboratory parameters
- Vital signs
- Physical examinations
-
Cognitive Measures
- MMSE: Mini-Mental State Examination
- CDR: Clinical Dementia Rating
- RBANS: Repeatable Battery for the Assessment of Neuropsychological Status
-
Functional Measures
- ADCS-ADL: Alzheimer's Disease Cooperative Study-Activities of Daily Living
- FAQ: Functional Activities Questionnaire
-
Biomarker Measures
- FDG-PET: Cerebral glucose metabolism changes
- CSF Biomarkers: Aβ42/40, p-tau, total tau, NfL
- Blood Biomarkers: Inflammatory markers, metabolic parameters
-
Imaging
- MRI brain volume measurements
- Connectivity analysis
The FDG-PET substudy is critical for demonstrating target engagement:
Imaging Protocol:
- Baseline and 52-week FDG-PET
- Regional analysis of glucose metabolism
- Focus on AD-vulnerable regions
Expected Findings:
- Attenuation of hypometabolism progression
- Improvement in specific regions
- Correlation with clinical outcomes
Cerebrospinal fluid collection enables:
- Amyloid Markers: Aβ42/40 ratio
- Tau Markers: Total tau, phosphorylated tau
- Neurodegeneration: Neurofilament light chain (NfL)
- Inflammatory Markers: Cytokines, chemokines
Blood-based markers for monitoring:
- Metabolic Parameters: Glucose, insulin, HbA1c
- Inflammatory Markers: IL-6, TNF-α
- Oxidative Stress: Antioxidant capacity
The benfotiamine trial represents advancement in several ways:
- Novel Mechanism: First Phase 2 trial of metabolic therapy in AD in years
- Different Approach: Provides alternative to amyloid-centric development
- Combination Potential: Could complement other therapeutic approaches
- Precision Medicine: May identify responders through biomarkers
If successful, benfotiamine could:
- Provide New Treatment Option: First metabolic therapy for AD
- Enable Combination: Work synergistically with amyloid-targeted agents
- Address Unmet Need: Help patients who don't respond to immunotherapy
- Improve Outcomes: Address cognitive and functional domains
Several metabolic approaches have been investigated in AD:
| Approach |
Developer |
Status |
Mechanism |
| Benfotiamine |
ATRI |
Phase 2 |
Thiamine activation |
| Pioglitazone |
Takeda |
Phase 3 (discontinued) |
PPARγ agonist |
| Metformin |
Various |
Phase 3 |
AMPK activation |
| ASL0413 |
AZ |
Phase 1 |
Lactate receptor |
The benfotiamine trial is distinguished by its focus on thiamine-dependent enzymes and comprehensive biomarker program.
¶ Safety and Tolerability
Benfotiamine has been used clinically for decades:
- Established Safety: Approved in Japan and other countries for diabetic complications
- Well-Tolerated: Generally mild side effects
- No Significant Interactions: Low drug-drug interaction potential
Based on previous studies:
- Common: GI upset (nausea, diarrhea)
- Less Common: Headache, dizziness
- Rare: Allergic reactions
The trial includes comprehensive monitoring:
- Regular physical examinations
- Laboratory assessments
- Adverse event documentation
- ECG monitoring (if indicated)
Benfotiamine has been studied in cognitive impairment:
MCI Trial (Gibson et al., 2013):
- 12-month randomized controlled trial
- 40 patients with MCI
- Significant improvement in cognitive scores
- Good safety and tolerability
Diabetes Studies:
- Improved cognitive scores in type 2 diabetes patients
- Reduced peripheral neuropathy complications
- Established brain penetration
Open-Label AD Studies:
- Preliminary evidence of cognitive benefit
- Improved cerebral metabolism on PET
- Safe and well-tolerated
The trial dose (300mg twice daily) was selected based on:
- Preclinical studies showing efficacy
- Human studies in other indications
- Brain exposure modeling
- Safety margins
¶ Challenges and Considerations
- Effect Size: Metabolic effects may be modest
- Patient Selection: Optimal responders unclear
- Biomarker Correlates: Need to establish target engagement markers
- Combination Strategy: Future combination with other agents
If Phase 2 is successful:
- Phase 3 trial with larger sample size
- Potential accelerated approval path
- Combination studies with amyloid antibodies
- Early intervention studies
- Prevention trials in at-risk populations
- Combination with disease-modifying agents
The exploration of thiamine (vitamin B1) in brain health dates back decades:
1930s-1950s:
- Thiamine discovered and characterized
- Early observations linking thiamine deficiency to neurological symptoms
- Beriberi research established thiamine's role in energy metabolism
1960s-1980s:
- Recognition of thiamine's role in brain function
- Animal studies demonstrating thiamine's impact on cognitive function
- Early post-mortem studies showing thiamine-dependent enzyme deficits in AD brain
1990s-2000s:
- Development of benfotiamine as a brain-penetrant thiamine derivative
- First clinical trials in diabetic neuropathy
- Growing interest in metabolic approaches to neurodegeneration
The thiamine hypothesis has evolved significantly over time:
Original Hypothesis (1970s-1980s):
- Thiamine deficiency as a cause of cognitive decline
- Supplementation as treatment
- Focus on Wernicke-Korsakoff syndrome relationship
Revised Hypothesis (2000s-present):
- Functional thiamine deficiency in AD (not absolute deficiency)
- Impaired thiamine-dependent enzyme activity
- Targeting upstream metabolic dysfunction
- Benfotiamine as the solution to brain penetration
Current Understanding (2020s):
- Thiamine-dependent enzyme deficits as a consequence of broader metabolic dysfunction
- Role in cerebral glucose hypometabolism
- Potential for combination with other metabolic modulators
- Integration with broader aging and metabolism research
Several metabolic approaches have been investigated in AD:
| Approach |
Developer |
Status |
Mechanism |
Evidence Level |
| Benfotiamine |
ATRI |
Phase 2 |
Thiamine activation |
Preclinical + Phase 1 |
| Pioglitazone |
Takeda |
Phase 3 (discontinued) |
PPARγ agonist |
Mixed |
| Metformin |
Various |
Phase 3 |
AMPK activation |
Extensive, neutral |
| ASL0413 |
AZ |
Phase 1 |
Lactate receptor |
Early |
| Diet ketone supplementation |
Various |
Research |
Ketone metabolism |
Preliminary |
The benfotiamine trial is distinguished by its focus on thiamine-dependent enzymes and comprehensive biomarker program.
Benfotiamine serves as a pro-drug that increases thiamine levels in the brain and activates critical thiamine-dependent enzymes. Thiamine is an essential cofactor for three key enzyme complexes in cerebral energy metabolism:
Enzyme Function:
- Catalyzes the conversion of pyruvate to acetyl-CoA
- Links glycolysis to the citric acid cycle (Krebs cycle)
- Rate-limiting step in glucose oxidation
AD-Associated Deficits:
- PDHC activity reduced by 40-70% in AD brain tissue
- Post-mortem studies show correlation with cognitive decline
- Activity inversely correlates with neurofibrillary tangle density
Therapeutic Implications:
- Benfotiamine directly activates PDHC
- Restoring activity could improve neuronal energy production
- May protect against excitotoxicity through improved energy reserve
Enzyme Function:
- Key rate-limiting enzyme in the citric acid cycle
- Catalyzes conversion of α-ketoglutarate to succinyl-CoA
- Generates NADH for ATP production
- Supports neurotransmitter synthesis (GABA, glutamate)
AD-Associated Deficits:
- Highly vulnerable to oxidative damage in AD
- Activity correlates directly with cognitive function
- One of the earliest enzymes affected in AD
Therapeutic Implications:
- α-KGDH supports mitochondrial energy production
- Restoration may improve neurotransmitter balance
- Protection against oxidative stress through NADPH production
Enzyme Function:
- Central enzyme in the pentose phosphate pathway
- Generates NADPH for antioxidant defense
- Supports lipid synthesis and cellular repair
- Connects glycolysis to nucleic acid synthesis
AD-Associated Deficits:
- Activity impaired in AD brain
- Reduced NADPH compromises antioxidant capacity
- Impairs cellular repair mechanisms
Therapeutic Implications:
- TK activation supports antioxidant defense
- May protect against oxidative stress in AD
- Supports cellular repair and membrane maintenance
The brain relies almost exclusively on glucose for energy, consuming approximately 20% of the body's glucose despite being only 2% of body weight. In Alzheimer's disease, this glucose metabolism is severely impaired:
Posterior Cingulate Cortex:
- Often the first region affected
- Critical for memory encoding and retrieval
- Hypometabolism detectable decades before diagnosis
- Strong correlation with amyloid burden
Temporal and Parietal Cortex:
- Progressive decline with disease
- Associated with language and spatial function
- Correlates with clinical severity
Prefrontal Cortex:
- Associated with executive dysfunction
- Affected in later disease stages
- Contributes to behavioral symptoms
Hippocampus:
- Early involvement in memory impairment
- Critical for memory consolidation
- Volume loss accompanies hypometabolism
Amyloid-Induced Dysfunction:
- Aβ oligomers directly impair glucose transporters
- Synaptic dysfunction reduces glucose demand
- Mitochondrial dysfunction impairs utilization
Tau-Related Changes:
- Neurofibrillary tangles correlate with hypometabolism
- Neuronal loss reduces metabolic demand
- Axonal dysfunction impairs glucose distribution
Vascular Contributions:
- Cerebral amyloid angiopathy affects blood flow
- Capillary dysfunction impairs delivery
- Neurovascular unit dysfunction
- Reduced ATP production compromises neuronal function
- Inability to maintain ion gradients disrupts neurotransmission
- Impaired cellular repair mechanisms accelerate neurodegeneration
- Vulnerable neurons are unable to withstand pathological insults
Beyond enzyme activation, benfotiamine provides additional benefits:
AGEs form when glucose or its metabolites modify proteins, lipids, or nucleic acids. In AD:
AGE Formation Pathways:
- Non-enzymatic glycation (Maillard reaction)
- Oxidative stress-driven formation
- Metabolism-driven modification
AGE Accumulation in AD Brain:
- Contributes to chronic inflammation through RAGE receptor activation
- Promotes protein cross-linking and aggregation
- Directly damages mitochondria
- Accelerates amyloid and tau pathology
Benfotiamine's Action:
- Inhibits AGE formation
- Reduces RAGE activation
- Decreases inflammatory signaling
Energy-deprived neurons are more vulnerable to Aβ toxicity:
Mechanisms of Protection:
- Improved ATP production supports cellular defense
- Reduced oxidative stress diminishes vulnerability
- Enhanced calcium regulation prevents toxicity
- Maintained cellular repair capacity
Evidence from Studies:
- Benfotiamine improves survival of neurons exposed to Aβ
- Reduces markers of oxidative stress
- Preserves synaptic function
Mitochondrial dysfunction triggers inflammatory responses:
Inflammatory Cascade:
- Damaged mitochondria release DAMPs
- Microglial activation
- Pro-inflammatory cytokine production
- Chronic neuroinflammation
Benfotiamine's Anti-inflammatory Effects:
- Reduces microglial activation
- Decreases pro-inflammatory cytokine production
- Supports anti-inflammatory pathways
- Reduces oxidative stress
The trial employs a randomized, double-blind, placebo-controlled design:
- Randomization: Ensures balanced groups for valid comparison
- Double-blind: Prevents bias in outcome assessment
- Placebo-controlled: Provides clear evidence of treatment effect
- Phase 2: Appropriate for signal detection before larger Phase 3 investment
Enrollment: 406 participants with early AD
- Sufficient for detecting moderate effect sizes
- Realistic for single-site trial
- Adequate for regulatory discussion
Randomization: 1:1 ratio to benfotiamine or placebo
- Equal probability of assignment
- Standard approach for Phase 2
- Enables straightforward statistical analysis
Duration: 52 weeks (1 year)
- Sufficient duration to detect metabolic effects
- Matches standard AD trial durations
- Allows for biomarker assessment
Dosing: Oral benfotiamine twice daily
- 300mg dose selected based on preclinical and clinical data
- Twice-daily to maintain stable blood levels
- Established as well-tolerated in previous studies
The trial enrolls patients with early-stage Alzheimer's disease:
Diagnosis: Probable AD per NIA-AA criteria
- Core clinical criteria for AD
- Excludes other causes of dementia
- Ensures homogeneous population
Stage: Mild cognitive impairment due to AD or mild AD dementia
- Early stage most likely to benefit
- Can complete all study procedures
- Clear baseline for measuring progression
Age: 50-85 years
- Appropriate age range for typical AD
- Excludes very early-onset (rare) and very late-onset (comorbidities)
MMSE: 20-26 (mild impairment)
- Ensures ability to complete assessments
- Excludes severe dementia (too advanced)
- Excludes very mild (floor/ceiling effects)
- Age 50-85 years
- Meet NIA-AA criteria for MCI due to AD or mild AD dementia
- MMSE score 20-26
- Confirmed amyloid pathology (PET or CSF)
- Stable on background AD medications (if applicable)
- Able to comply with study procedures
- Significant neurological disease other than AD
- Psychiatric conditions that could affect assessment
- Active cancer or life-threatening medical conditions
- Contraindications to study medication
- Previous thiamine supplementation (within 3 months)
- Significant renal or hepatic impairment
¶ Primary and Secondary Endpoints Deep Dive
Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)
The ADAS-Cog is the gold standard for cognitive assessment in AD trials:
11-item version assesses:
- Word recall: Immediate and delayed recall of 10 words
- Naming: Name objects and fingers
- Commands: Follow spoken commands
- Construction: Copy two overlapping pentagons
- Ideational praxia: Mail a letter
- Orientation: Date, time, place
- Word recognition: Identify learned words
- Remembering instructions: Follow spoken instructions
- Spoken language: Describe picture
- Word finding difficulty: Name items
- Comprehension: Respond to questions
Scoring:
- Higher scores indicate greater impairment
- Score range: 0-70 (typical)
- Clinically meaningful change: 4-6 points
- Minimum detectable change: ~2 points
Safety and Tolerability
Comprehensive safety assessment:
- Adverse event monitoring
- Laboratory parameters
- Vital signs
- Physical examinations
-
Cognitive Measures
- MMSE: Mini-Mental State Examination
- CDR: Clinical Dementia Rating
- RBANS: Repeatable Battery for the Assessment of Neuropsychological Status
-
Functional Measures
- ADCS-ADL: Alzheimer's Disease Cooperative Study-Activities of Daily Living
- FAQ: Functional Activities Questionnaire
-
Biomarker Measures
- FDG-PET: Cerebral glucose metabolism changes
- CSF Biomarkers: Aβ42/40, p-tau, total tau, NfL
- Blood Biomarkers: Inflammatory markers, metabolic parameters
-
Imaging
- MRI brain volume measurements
- Connectivity analysis
The FDG-PET substudy is critical for demonstrating target engagement:
- Baseline and 52-week FDG-PET
- Regional analysis of glucose metabolism
- Focus on AD-vulnerable regions
- Attenuation of hypometabolism progression
- Improvement in specific regions
- Correlation with clinical outcomes
FDG-PET directly measures the mechanism of benfotiamine action:
- Restoration of thiamine-dependent enzyme activity
- Improved cerebral glucose metabolism
- Correlation with cognitive outcomes
This makes FDG-PET the ideal biomarker for demonstrating target engagement.
Cerebrospinal fluid collections enable:
- Aβ42/40 ratio: Confirms amyloid pathology
- Changes with treatment may indicate downstream effects
- Total tau: Marker of neuronal damage
- Phospho-tau: Marker of tau pathology
- Neurofilament light chain (NfL): Marker of axonal injury
- May be reduced with neuroprotection
- Cytokines, chemokines: Measure neuroinflammation
- May be reduced with benfotiamine's anti-inflammatory effects
Blood-based markers for monitoring:
- Glucose, insulin, HbA1c: Metabolic status
- Thiamine levels: Compliance marker
- IL-6, TNF-α: Pro-inflammatory cytokines
- May be reduced with treatment
- Antioxidant capacity: Measure of oxidative stress
- May improve with treatment
¶ Safety and Tolerability Deep Dive
Benfotiamine has been used clinically for decades:
Established Safety:
- Approved in Japan and other countries for diabetic complications
- Decades of clinical use
- Well-characterized safety profile
Well-Tolerated:
- Generally mild side effects
- Low discontinuation rates
- No significant organ toxicity
No Significant Interactions:
- Low drug-drug interaction potential
- Non-CYP metabolism
- Safe in hepatic impairment
Based on previous studies:
Common (≥1%):
- GI upset (nausea, diarrhea)
- Usually mild and transient
- May improve with food
Less Common (<1%):
- Headache
- Dizziness
- Generally not treatment-limiting
Rare:
- Allergic reactions
- Discontinue if occurs
The trial includes comprehensive monitoring:
- Regular physical examinations
- Laboratory assessments
- Adverse event documentation
- ECG monitoring (if indicated)
- MRI for safety (if indicated)
| Treatment |
Class |
Key Safety Concerns |
Serious AE Rate |
| Benfotiamine |
Metabolic |
GI upset |
Low |
| Lecanemab |
Anti-amyloid |
ARIA (brain edema) |
~12% |
| Donanemab |
Anti-amyloid |
ARIA (brain edema) |
~24% |
| Donepezil |
Cholinesterase inhibitor |
GI, bradycardia |
Low |
| Memantine |
NMDA antagonist |
Dizziness, headache |
Low |
¶ Proteins and Genes