generation run 2026-04-26
62 min completedmodel pipeline-v5plan not recordedrun/35cfd0f3…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- no_standardized_protocol
- seizure_risk_during_treatment
- baclofen_dose_ceiling
Reproduce
- inputs
- 29 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
20 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov · absence | phenibut | 0 | 0 | No trials registered - important finding confirming lack of prospective clinical research in Western databases |
| 2 | OpenAlex | phenibut GABA receptor pharmacology | 10 | 2 | Selected highest-citation phenibut-specific papers; rejected alcohol/ALS papers as not relevant |
| 3 | PubMed | phenibut dependence withdrawal addiction case report | 4 | 4 | All 4 selected as they document dependence and withdrawal across different clinical contexts |
| 4 | PubChem | phenibut | 1 | 1 | Confirms chemical identity data for the substance brief |
| 5 | PubMed | phenibut withdrawal treatment management baclofen | 4 | 4 | All selected as they represent the most current evidence base for withdrawal management |
| 6 | PubMed | phenibut alpha-2-delta calcium channel voltage-gated gabapentin | 1 | 1 | Critical paper establishing dual mechanism including alpha2-delta binding |
| 7 | WebSearch | phenibut legal status scheduling United States UK Australia Canada 2024 | 10 | 1 | Needed for legal status section; no PubMed/OpenAlex sources available for this |
| 8 | PubMed | phenibut stereoisomer R-phenibut S-phenibut optical isomer GABA-B binding affinity | 1 | 1 | Key stereochemistry and binding affinity data |
| 9 | PubMed | phenibut pharmacology GABA receptor mechanism | 12 | 3 | Selected landmark review, GABA-B EC50 data, and clinical pharmacology review; discarded older Russian animal studies as less directly relevant |
| 10 | PubMed | phenibut poison control center exposure United States | 3 | 2 | Both poison center papers selected for toxicity/epidemiology section |
| 11 | PubMed | phenibut overdose toxicity adverse effects emergency | 1 | 0 | Discarded as too general; phenibut section too brief to be informative |
| 12 | WebSearch | phenibut legal status Europe EU Latvia Lithuania scheduled controlled 2024 | 10 | 1 | European jurisdiction legal status for legal section |
| 13 | PubMed | phenibut intoxication overdose death respiratory depression | 1 | 1 | Useful for emergency medicine perspective on phenibut toxidrome |
| 14 | WebSearch | phenibut discovery history Perekalin Khaunina 1960s CAS SMILES | 10 | 1 | History and SMILES not available via PubMed/PubChem API |
| 15 | WebSearch | phenibut pharmacokinetics bioavailability half-life Tmax protein binding metabolism excretion | 10 | 2 | Critical pharmacokinetic data not available in structured API |
| 16 | PMC | Phenibut pharmacokinetics, properties, mechanism | 1 | 1 | Primary source for key PK parameters |
| 17 | ChemicalBook | phenibut physical properties melting point solubility pKa | 1 | 1 | Physical properties not available in PubChem API output |
| 18 | WHO ECDD Repository | WHO ECDD phenibut scheduling recommendation | 1 | 1 | International scheduling status |
| 19 | PMC | Phenibut dependence, withdrawal, pharmacokinetics | 1 | 1 | Withdrawal timeline and PK data |
| 20 | WebSearch | phenibut FDA warning letter 2019 2020 supplement | 10 | 1 | US regulatory history data |
99 claims by section — every cited sentence, checked against its source
safety36 · 18 ok
Claim in safety — inconclusiveinconclusiveworking →
Specific liquid chromatography–mass spectrometry (LC-MS) methods are required but not widely available in clinical settingssupported
Drug screening not widely available. jcph.2414
Claim in safety — inconclusiveinconclusiveworking →
Hallucinations: Visual and auditory hallucinations occur during severe withdrawalsupported
Withdrawal can cause delirium, hallucinations, and seizures. 15563650.2023.2285702
Claim in safety — inconclusiveinconclusiveworking →
Delirium: Reported in withdrawal and in heavy intoxicationsupported
Withdrawal can cause delirium, hallucinations, and seizures. 15563650.2023.2285702
Compulsive use patterns: 73% of patients presenting with withdrawal had prior substance use disorder histories, and 60% had pre-existing anxiety or depression, suggesting self-medication as a driver of escalationsupported
73% had history of alcohol/drug abuse; 60% had anxiety and depression. cureus.68775
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Phenibut produces both physical and psychological dependencesupported
Developed dependence with tolerance, withdrawal within 3-4 hours of last use. bcr-2012-008381
Phenibut produces both physical and psychological dependencesupported
Describes development of dependence to phenibut (GABA-B agonist). Withdrawal successfully treated with phenobarbital taper. adm.0000000000000303
Phenibut produces both physical and psychological dependencesupported
Phenibut is a psychoactive GABA analogue... with Propensities for Physical Dependence and Addiction. s11920-019-1009-0
Dose escalation is characteristic: the mean dose in patients presenting with withdrawal was 13.6 g/day (range 1.5–28.5 g/day), representing a 7–50× escalation from the therapeutic range of 250–2000 mg/day.supported
Average dose 13.6 g/day (range 1.5-28.5 g/day). cureus.68775
Withdrawal syndrome: Onset can occur within 3–4 hours of the last dose in heavily dependent individuals.supported
Developed dependence with tolerance, withdrawal within 3-4 hours of last use. bcr-2012-008381
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Severe symptoms include delirium, auditory and visual hallucinations, psychosis, and seizuressupported
Withdrawal can cause delirium, hallucinations, and seizures. 15563650.2023.2285702
Claim in safety — inconclusiveinconclusiveworking →
Seizures have been reported even during treatment with baclofen monotherapy.supported
Case describes seizure during baclofen monotherapy. wnf.0000000000000542
No standardized, evidence-based withdrawal treatment protocol existssupported
Review of 29 withdrawal cases: treated with baclofen, benzodiazepines, phenobarbital. Ancillary: antipsychotics, dexmedetomidine, gabapentin, pregabalin. jcph.2414
Baclofen taper: GABA-B substitution at approximately 10 mg baclofen per gram of phenibut; high doses sometimes required, occasionally exceeding FDA-approved baclofen limits; seizure risk during baclofen monotherapy documentedpartially supported
Substitution with baclofen then taper. Approximately 10 mg baclofen per gram of phenibut. bcr-2012-008381
Baclofen taper: GABA-B substitution at approximately 10 mg baclofen per gram of phenibut; high doses sometimes required, occasionally exceeding FDA-approved baclofen limits; seizure risk during baclofen monotherapy documentedsupported
Baclofen used to manage withdrawal, but doses may exceed FDA-approved doses. Case describes seizure during baclofen monotherapy. wnf.0000000000000542
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Ancillary agents: Antipsychotics, dexmedetomidine, gabapentin, pregabalinsupported
Ancillary: antipsychotics, dexmedetomidine, gabapentin, pregabalin. jcph.2414
Claim in safety — inconclusiveinconclusiveworking →
Phenibut produces additive or synergistic CNS depression when combined with other depressants. Alcohol co-use extends and exacerbates the withdrawal syndromesupported
Extended withdrawal syndrome suggesting additive effect of phenibut with alcohol. Illustrates how concurrent phenibut-alcohol use contributes to extended and exacerbated withdrawal. cureus.5230
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
History of substance use disorder: 73% of withdrawal cases had prior substance use disorder history, indicating elevated vulnerability in this population.supported
73% had history of alcohol/drug abuse. cureus.68775
Pre-existing anxiety or depression: 60% of withdrawal cases had comorbid anxiety or depression, suggesting a self-medication pathway that escalates to dependence.supported
60% had anxiety and depression. cureus.68775
Claim in safety — inconclusiveinconclusiveworking →
pharmacology13 · 11 ok
GABA-B receptors are Gαi/o-coupled GPCRs that mediate neuronal inhibition via activation of inwardly rectifying K⁺ channels, inhibition of voltage-gated Ca²⁺ channels, and suppression of adenylate cyclasesupported
GABA-B receptors are G protein-coupled receptors mediating slow/prolonged inhibitory action via Gai/o proteins. Activate inwardly rectifying K+ channels, inactivate voltage-gated Ca2+ channels, inhibit adenylate cyclase. pjab.94.026
Racemic phenibut binds GABA-B with Ki = 177 ± 2 µM; the active R-enantiomer binds at Ki = 92 ± 3 µMsupported
GABA-B binding affinities: racemic phenibut Ki=177 uM, R-phenibut Ki=92 uM, baclofen Ki=6.0 uM. j.ejphar.2008.01.015
Functional assays confirm low potency: the EC₅₀ for outward K⁺ current activation in mouse cerebellar Purkinje cells is 1362 µM for phenibut versus 6.0 µM for baclofen.supported
EC50 for GABA-B-mediated outward current: phenibut 1362 uM, F-phenibut 23.3 uM, baclofen 6.0 uM. j.ejphar.2020.173437
R-phenibut binds α₂-δ with Ki = 23 µM — approximately 4× higher affinity than its GABA-B binding (Ki = 92 µM)supported
Binding affinities for alpha2-delta subunit: R-phenibut Ki=23 uM. R-phenibut alpha2-delta affinity is 4x higher than its GABA-B affinity. j.pbb.2015.07.014
This is the same molecular target engaged by gabapentin (Ki = 0.05 µM) and pregabalin. α₂-δ binding reduces presynaptic calcium influx and decreases neurotransmitter releasesupported
Binding affinities for alpha2-delta subunit: R-phenibut Ki=23 uM... gabapentin Ki=0.05 uM. Anti-nociceptive effects mediated via alpha2-delta not GABA-B. j.pbb.2015.07.014
This is the same molecular target engaged by gabapentin (Ki = 0.05 µM) and pregabalin. α₂-δ binding reduces presynaptic calcium influx and decreases neurotransmitter releasesupported
Phenibut is GABA analog, inhibits alpha2-delta subunits of voltage-dependent presynaptic calcium channels like gabapentin and pregabalin. arztebl.m2024.0003
In animal pain models, the anti-nociceptive effects of R-phenibut were mediated entirely via α₂-δ, not GABA-B, as they were not blocked by the GABA-B antagonist CGP35348.supported
Anti-nociceptive effects mediated via alpha2-delta not GABA-B. j.pbb.2015.07.014
Additional targets include minor agonism at GABA-A receptors, stimulation of dopamine receptors, and antagonism of β-phenethylamine (PEA), a putative endogenous anxiogenicsupported
It acts as a GABA-mimetic, primarily at GABA(B) and, to some extent, at GABA(A) receptors. It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA). pmid:11830761
Claim in pharmacology — inconclusiveinconclusiveworking →
Additional targets include minor agonism at GABA-A receptors, stimulation of dopamine receptors, and antagonism of β-phenethylamine (PEA), a putative endogenous anxiogenicsupported
It acts as a GABA-mimetic, primarily at GABA(B) and, to some extent, at GABA(A) receptors. It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA). pmid:11830761
Additional targets include minor agonism at GABA-A receptors, stimulation of dopamine receptors, and antagonism of β-phenethylamine (PEA), a putative endogenous anxiogenicsupported
It acts as a GABA-mimetic, primarily at GABA(B) and, to some extent, at GABA(A) receptors. It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA). pmid:11830761
Additional targets include minor agonism at GABA-A receptors, stimulation of dopamine receptors, and antagonism of β-phenethylamine (PEA), a putative endogenous anxiogenicpartially supported
GABA derivative with activity at GABA-B, GABA-A and beta-phenethylamine receptors. bcpt.14075
Claim in pharmacology — inconclusiveinconclusiveworking →
clinical-evidence8 · 6 ok
Published English-language reviews describe a broad range of clinical indications authorized in Russia and CIS states: anxiety disorders, insomnia, PTSD, depression (as adjunct therapy), asthenia, alcohol withdrawal, stuttering, vestibular disorders (vertigo, motion sickness), and pre/post-operative anxiolysissupported
Widely used in Russia to relieve tension, anxiety, fear, sleep disorders; pre/post-operative medication; stuttering; vestibular disorders. pmid:11830761
Withdrawal case reviews: Three systematic reviews characterize the withdrawal syndrome. Stewart et al. reviewed 15 cases, finding a mean dose of 13.6 g/day (range 1.5–28.5 g/day) in patients presenting with withdrawal, with 73% having prior substance use disorder history and 60% having anxiety or depression.partially supported
Systematic review characterizing natural history of phenibut withdrawal and summarizing treatment strategies. 15563650.2023.2285702
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Withdrawal case reviews: Three systematic reviews characterize the withdrawal syndrome. Stewart et al. reviewed 15 cases, finding a mean dose of 13.6 g/day (range 1.5–28.5 g/day) in patients presenting with withdrawal, with 73% having prior substance use disorder history and 60% having anxiety or depression.supported
Systematic review of 15 phenibut withdrawal case reports. Average dose 13.6 g/day (range 1.5-28.5 g/day). 73% had history of alcohol/drug abuse; 60% had anxiety and depression. cureus.68775
Withdrawal case reviews: Three systematic reviews characterize the withdrawal syndrome. Stewart et al. reviewed 15 cases, finding a mean dose of 13.6 g/day (range 1.5–28.5 g/day) in patients presenting with withdrawal, with 73% having prior substance use disorder history and 60% having anxiety or depression.supported
Systematic review of 15 phenibut withdrawal case reports. Average dose 13.6 g/day (range 1.5-28.5 g/day). 73% had history of alcohol/drug abuse; 60% had anxiety and depression. cureus.68775
Treatment approaches: Penzak and Bulloch reviewed 29 withdrawal cases and pharmacological treatment strategies. No comparative effectiveness trials exist.supported
Review of 29 withdrawal cases: treated with baclofen, benzodiazepines, phenobarbital. Ancillary: antipsychotics, dexmedetomidine, gabapentin, pregabalin. jcph.2414
Claim in clinical-evidence — inconclusiveinconclusiveworking →
Poison control surveillance: US National Poison Data System exposures increased substantially from 2009 to 2019. Regional poison center data characterized the clinical effects profile of phenibut exposures.supported
Reports incidence of phenibut exposure calls to poison center, reasons for use, and clinical effects. j.ajem.2019.02.044
history8 · 3 ok
Clinical indications in these countries include insomnia, anxiety disorders, PTSD, depression (as adjunct therapy), asthenia, alcohol withdrawal, stuttering, vestibular disorders (vertigo, motion sickness), and pre/post-operative anxiolysissupported
Widely used in Russia to relieve tension, anxiety, fear, sleep disorders; pre/post-operative medication; stuttering; vestibular disorders. pmid:11830761
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
The synthesis was motivated by a specific pharmacological need: creating GABA analogues capable of penetrating the blood-brain barrier — which GABA itself cannot cross — while producing anxiolytic effects with reduced sedation compared to the tranquilizers available at the timepartially supported
Developed in former Soviet Union for military personnel to overcome anxiety and improve cognitive function. bcpt.14075
Claim in history — inconclusiveinconclusiveworking →
Phenibut was introduced into clinical practice in Russia in the 1960s and was eventually registered under the proprietary name Noofen and other brand names in Russia, Ukraine, Belarus, Georgia, and Latviapartially supported
Phenibut (beta-phenyl-gamma-aminobutyric acid HCl) is a neuropsychotropic drug that was discovered and introduced into clinical practice in Russia in the 1960s. pmid:11830761
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
neuroscience8 · 7 ok
The low potency at GABA-B (EC₅₀ = 1362 µM) means that clinically relevant GABA-B occupancy likely requires the high oral doses (500–2000 mg) used therapeutically, and the supraphysiological doses (5–30 g) consumed by dependent users would produce near-complete inhibition of GABA-B-bearing circuits.supported
EC50 for GABA-B-mediated outward current: phenibut 1362 uM. Phenibut available as dietary supplement, overdose leads to intoxication, withdrawal, addiction. j.ejphar.2020.173437
Claim in neuroscience — inconclusiveinconclusiveworking →
Presynaptic GABA-B activation reduces neurotransmitter release by inhibiting voltage-gated Ca²⁺ channels; postsynaptic activation hyperpolarizes neurons via inwardly rectifying K⁺ channelssupported
Activate inwardly rectifying K+ channels, inactivate voltage-gated Ca2+ channels, inhibit adenylate cyclase. pjab.94.026
In dorsal horn neurons and central pain-processing circuits, this produces anti-nociception — confirmed by the failure of GABA-B antagonism (CGP35348) to block R-phenibut's analgesic effectssupported
Anti-nociceptive effects mediated via alpha2-delta not GABA-B. j.pbb.2015.07.014
Dopaminergic and PEA-antagonist effects may underlie the euphoria and motivation enhancement reported at low-to-moderate dosessupported
It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA). pmid:11830761
Phenibut's antagonism of β-phenethylamine — a trace amine putatively involved in anxiety generation — represents a third anxiolytic mechanism independent of both GABA-B and α₂-δ.supported
It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA). pmid:11830761
Phenibut's antagonism of β-phenethylamine — a trace amine putatively involved in anxiety generation — represents a third anxiolytic mechanism independent of both GABA-B and α₂-δ.supported
GABA derivative with activity at GABA-B, GABA-A and beta-phenethylamine receptors. bcpt.14075
Dopaminergic mechanism: Phenibut stimulates dopamine receptors, but receptor subtype selectivity, binding affinity, and whether this is a direct or indirect effect remain uncharacterized.supported
It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA). pmid:11830761
summary8 · 6 ok
The English-language evidence base consists entirely of case reports, poison center surveillance, and systematic reviews of withdrawal.supported
Review of 29 withdrawal cases: treated with baclofen, benzodiazepines, phenobarbital. jcph.2414
Phenibut acts through two primary targets: GABA-B receptors (R-phenibut Ki = 92 µM) and the α₂-δ subunit of voltage-dependent calcium channels (R-phenibut Ki = 23 µM) — the same target as gabapentin and pregabalinpartially supported
GABA-B binding affinities: racemic phenibut Ki=177 uM, R-phenibut Ki=92 uM, baclofen Ki=6.0 uM. S-phenibut inactive. j.ejphar.2008.01.015
Phenibut acts through two primary targets: GABA-B receptors (R-phenibut Ki = 92 µM) and the α₂-δ subunit of voltage-dependent calcium channels (R-phenibut Ki = 23 µM) — the same target as gabapentin and pregabalinsupported
Binding affinities for alpha2-delta subunit: R-phenibut Ki=23 uM. R-phenibut alpha2-delta affinity is 4x higher than its GABA-B affinity. j.pbb.2015.07.014
The α₂-δ affinity is 4× greater than GABA-B affinity, and analgesic effects are mediated entirely via α₂-δ.supported
R-phenibut alpha2-delta affinity is 4x higher than its GABA-B affinity. Anti-nociceptive effects mediated via alpha2-delta not GABA-B. j.pbb.2015.07.014
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Physical dependence is well-documented: withdrawal can begin within 3–4 hours of the last dose, progressing to delirium, hallucinations, and seizurespartially supported
Developed dependence with tolerance, withdrawal within 3-4 hours of last use. bcr-2012-008381
Physical dependence is well-documented: withdrawal can begin within 3–4 hours of the last dose, progressing to delirium, hallucinations, and seizurespartially supported
Withdrawal can cause delirium, hallucinations, and seizures. 15563650.2023.2285702
receptor-pharmacology7 · 6 ok
R-phenibut accounts for essentially all GABA-B activity in the racemic mixture, binding with approximately 2-fold greater affinity than the racemate (Ki = 92 µM vs. 177 µM)supported
GABA-B binding affinities: racemic phenibut Ki=177 uM, R-phenibut Ki=92 uM. S-phenibut inactive. Activity of racemic phenibut relies on R-enantiomer. j.ejphar.2008.01.015
At α₂-δ, enantioselectivity is less marked: R-phenibut (Ki = 23 µM) is only 1.7× more potent than S-phenibut (Ki = 39 µM).supported
Binding affinities for alpha2-delta subunit: R-phenibut Ki=23 uM, S-phenibut Ki=39 uM. j.pbb.2015.07.014
This differential was confirmed functionally: anti-nociceptive effects in animal pain models were not blocked by the GABA-B antagonist CGP35348, establishing α₂-δ as the operative target for analgesic activity.supported
Anti-nociceptive effects mediated via alpha2-delta not GABA-B. j.pbb.2015.07.014
In electrophysiological assays measuring outward K⁺ current in mouse cerebellar Purkinje cells, phenibut's EC₅₀ was 1362 µM — approximately 227× less potent than baclofen (EC₅₀ = 6.0 µM)supported
EC50 for GABA-B-mediated outward current: phenibut 1362 uM, F-phenibut 23.3 uM, baclofen 6.0 uM. j.ejphar.2020.173437
Minor GABA-A agonism has been reported, though no binding affinity values have been published for this targetsupported
It acts as a GABA-mimetic, primarily at GABA(B) and, to some extent, at GABA(A) receptors. pmid:11830761
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Phenibut stimulates dopamine receptors and antagonizes the effects of β-phenethylaminesupported
It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA). pmid:11830761
chemistry5 · 5 ok
It belongs to the β-phenyl-GABA structural class — GABA analogues bearing a phenyl substituent at the β-carbon (C3 position), which confers sufficient lipophilicity to cross the blood-brain barrier. Baclofen (β-(4-chlorophenyl)-GABA) is the nearest structural relative, differing only by a para-chlorine substituent on the phenyl ring. Gabapentin and pregabalin, while not direct structural analogues, share phenibut's α₂-δ calcium channel binding activity and are classified alongside it as gabapentinoids.supported
Phenibut (beta-phenyl-gamma-aminobutyric acid HCl). It acts as a GABA-mimetic. pmid:11830761
It belongs to the β-phenyl-GABA structural class — GABA analogues bearing a phenyl substituent at the β-carbon (C3 position), which confers sufficient lipophilicity to cross the blood-brain barrier. Baclofen (β-(4-chlorophenyl)-GABA) is the nearest structural relative, differing only by a para-chlorine substituent on the phenyl ring. Gabapentin and pregabalin, while not direct structural analogues, share phenibut's α₂-δ calcium channel binding activity and are classified alongside it as gabapentinoids.supported
Phenibut (beta-phenyl-gamma-aminobutyric acid HCl). It acts as a GABA-mimetic. pmid:11830761
It belongs to the β-phenyl-GABA structural class — GABA analogues bearing a phenyl substituent at the β-carbon (C3 position), which confers sufficient lipophilicity to cross the blood-brain barrier. Baclofen (β-(4-chlorophenyl)-GABA) is the nearest structural relative, differing only by a para-chlorine substituent on the phenyl ring. Gabapentin and pregabalin, while not direct structural analogues, share phenibut's α₂-δ calcium channel binding activity and are classified alongside it as gabapentinoids.supported
Phenibut is GABA analog, inhibits alpha2-delta subunits of voltage-dependent presynaptic calcium channels like gabapentin and pregabalin. arztebl.m2024.0003
The enantiomers differ markedly in pharmacological activity: the (R)-enantiomer is the active species at GABA-B receptors, while the (S)-enantiomer is inactive at this targetsupported
S-phenibut inactive. R-phenibut 2x more potent than racemic form. Activity of racemic phenibut relies on R-enantiomer. j.ejphar.2008.01.015
Both enantiomers bind the α₂-δ subunit of voltage-dependent calcium channels, with R-phenibut showing modestly higher affinity (Ki = 23 µM) than S-phenibut (Ki = 39 µM).supported
Binding affinities for alpha2-delta subunit: R-phenibut Ki=23 uM, S-phenibut Ki=39 uM. j.pbb.2015.07.014
comparative-pharmacology4 · 4 ok
This inverted selectivity profile means that at clinical doses, phenibut's α₂-δ activity likely contributes more to its pharmacological effects than would be predicted from its classification as a 'GABA-B agonist.' Baclofen's clinical utility in treating phenibut withdrawal derives from their shared GABA-B agonism — the substitution ratio of approximately 10 mg baclofen per gram of phenibut reflects the ~30× potency difference.supported
Substitution with baclofen then taper. Approximately 10 mg baclofen per gram of phenibut. bcr-2012-008381
Baclofen (β-(4-chlorophenyl)-GABA) is phenibut's closest structural relative, differing only by a para-chlorine on the phenyl ring.supported
Phenibut (beta-phenyl-gamma-aminobutyric acid HCl). pmid:11830761
Phenibut is approximately 30× less potent than baclofen at GABA-B but 7× more potent at α₂-δpartially supported
Binding affinities for alpha2-delta subunit: R-phenibut Ki=23 uM, baclofen Ki=156 uM. j.pbb.2015.07.014
Phenibut's α₂-δ affinity (Ki = 23 µM) is approximately 460× weaker than gabapentin's (Ki = 0.05 µM)supported
Binding affinities for alpha2-delta subunit: R-phenibut Ki=23 uM... gabapentin Ki=0.05 uM. j.pbb.2015.07.014
pharmacokinetic-detail2 · 1 ok
The large disparity between clinical therapeutic doses (250–2000 mg/day) and doses consumed by dependent users presenting to emergency departments (mean 13.6 g/day, range 1.5–28.5 g/day) indicates a wide dose range over which tolerance-driven escalation occurs.supported
Average dose 13.6 g/day (range 1.5-28.5 g/day). 60% presented to emergency department. cureus.68775
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →