Phenylpiracetam: The Complete Scientific Guide

🧬 What is Phenylpiracetam? Complete Identification

Phenylpiracetam is a synthetic racetam nootropic with the molecular formula C12H14N2O2 and was first synthesized and reported in 1983 in the USSR.

Medical definition: Phenylpiracetam (also known by trade names Phenotropil, Carphedon, and research code RS-1665) is a 2-pyrrolidone (racetam-class) derivative in which a phenyl group is substituted at the 4-position of the pyrrolidone ring; this substitution increases lipophilicity and alters pharmacodynamics relative to piracetam.

• Alternative names: Phenylpiracetam, Phenotropil, Carphedon, RS-1665.
• Classification: Nootropics / racetam-class cognitive enhancer; psychostimulant-like racetam derivative.
• Chemical formula: C12H14N2O2.
• IUPAC: 2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide.

📜 History and Discovery

Phenylpiracetam was reported and developed in the Soviet Union in 1983 as a modified piracetam analogue investigated for cognitive deficits and stress resilience.

• 1970s–1983: Medicinal chemistry programs in the USSR developed many racetam analogs; phenyl-substituted derivatives were pursued to improve blood–brain barrier penetration and potency.
• 1983: Phenylpiracetam described in Russian pharmacologic reports and introduced into clinical practice for short-term cognitive impairment, asthenia, and enhancement of tolerance to physical/psychological stressors.
• 1990s–2000s: Clinical/preclinical Russian literature expands; product names Phenotropil and Carphedon become known in post-Soviet clinical settings.
• 2010s–present: Appears on international nootropic markets and in sports-doping discussions; robust, modern English-language RCTs remain scarce.

Note: Many early primary reports are in Russian-language journals; English-language, PubMed-indexed randomized trials for phenylpiracetam are limited. If you require retrieval of original Russian/translated studies, I can perform a targeted literature pull on request.

⚗️ Chemistry and Biochemistry

The phenyl substitution at the 4-position confers increased lipophilicity and improved blood–brain barrier penetration compared with piracetam, which correlates with increased potency and stimulant-like effects.

Molecular structure

• Core: 2-oxo-pyrrolidine (gamma-lactam) scaffold.
• Substitutions: Phenyl at 4-position; acetamide at N1.
• Functional groups: Amide (H-bond donor/acceptor), keto (carbonyl), aromatic ring (increased hydrophobicity).

Physicochemical properties

• Appearance: White to off-white crystalline powder.
• Solubility: Moderate water solubility; more lipophilic than piracetam. Soluble in ethanol and DMSO.
• Estimated logP: Moderate (approx. ~0.5–1.5 by analogy to supplier data).
• Molar mass: 218.25 g·mol−1.

Dosage forms

• Immediate-release tablets
• Gelatin/vegetarian capsules (powder)
• Compounded oral solutions/suspensions (rare)
• Research/crystallized salts and polymorphs (laboratory grade)

Stability & storage

• Store: Dry, cool, protected from light (15–25°C) in airtight containers.
• Shelf life: Manufacturer- and excipient-dependent; typical reagent-grade stability >2 years if stored correctly.

💊 Pharmacokinetics: The Journey in Your Body

Phenylpiracetam is orally absorbed with a reported time-to-peak concentration approximately 1–2 hours and an estimated elimination half-life in humans of approximately 3–5 hours.

Absorption and Bioavailability

Primary absorption occurs in the small intestine via passive diffusion; increased lipophilicity speeds transcellular uptake vs piracetam, producing a faster onset.

• Tmax: ~1–2 hours (estimate from clinical series and racetam analog comparisons).
• Oral bioavailability: No authoritative absolute human % published; estimated moderate-to-good (approx. 50–90% by analogy to racetam-class compounds).
• Influencing factors: Food (delays Tmax, may reduce Cmax), formulation, GI motility, renal function.

Distribution and Metabolism

Phenylpiracetam crosses the blood–brain barrier and distributes into CNS tissue; metabolic pathways in humans are not well-characterized in English-language literature.

• BBB penetration: Yes — phenyl substitution increases CNS penetration relative to piracetam.
• Volume of distribution: Not well-defined; racetam-class drugs typically show moderate Vd with CNS distribution.
• Metabolism: Partial hepatic metabolism probable; specific CYP isoforms not robustly identified in available sources.

Elimination

Renal excretion is a major elimination route for racetam drugs; phenylpiracetam and its metabolites are substantially cleared within 24–48 hours in subjects with normal renal function.

• Half-life: Estimated ~3–5 hours.
• Elimination: Primarily renal (parent and metabolites), minor biliary possible.
• Clinical implication: Dose reduction or avoidance advised in significant renal impairment.

🔬 Molecular Mechanisms of Action

Phenylpiracetam exerts multimodal neuropharmacologic effects — enhanced dopaminergic and cholinergic signaling, modulation of glutamatergic neurotransmission and improved neuronal metabolic resilience — although human molecular confirmation is limited.

• Cellular targets: Neuronal membrane-associated proteins that modulate neurotransmitter systems and synaptic plasticity.
• Neurotransmitter effects: Increased dopaminergic and noradrenergic tone (preclinical data), indirect facilitation of cholinergic signaling, modulation of glutamate/GABA balance.
• Signaling pathways: Putative enhancement of synaptic plasticity-related cascades, improved mitochondrial/energy handling under stress in animal models.
• Gene expression: No robust human transcriptomic mapping; animal studies suggest modulation of plasticity-related genes, but human data are lacking.

✨ Science-Backed Benefits

Evidence across reported effects is generally rated as low-to-moderate due to scarcity of high-quality randomized trials in English; many claims rest on small clinical series and preclinical work.

🎯 Cognitive enhancement (attention & processing speed)

Evidence Level: Low-to-moderate

• Physiology: Enhances cortical activation and neurotransmission in attention networks, consistent with improved sustained attention and faster processing.
• Molecular mechanism: Augmented dopaminergic/noradrenergic tone and cholinergic facilitation of prefrontal circuits.
• Target: Healthy adults seeking short-term cognitive enhancement; patients with mild post-injury cognitive deficits (per Russian series).
• Onset: Subjective within 30–120 minutes; measurable in short cognitive tasks acutely.

Clinical Study: Most human trial data are small-scale and in Russian-language literature; few modern, PubMed-indexed randomized controlled trials exist. A systematic English-language evidence base is not yet robust. I can retrieve specific original-study citations on request.

🎯 Anti-fatigue and physical tolerance

Evidence Level: Low-to-moderate

• Physiology: Increased central arousal and motivation reduce perceived exertion; animal data show improved performance under stress.
• Target: Individuals requiring short-term anti-fatigue effects; operational users (non-competitive contexts).
• Onset: Acute; during hours after dosing.

Clinical Study: Evidence mainly from preclinical and small human series; no definitive modern RCT to quantify effect size in percentage terms is available in the English literature as of this dossier.

🎯 Cognitive rehabilitation after stroke/TBI

Evidence Level: Low

• Physiology: Proposed support of synaptic plasticity and resilience to ischemic stress may facilitate recovery.
• Onset: Reported benefits usually after repeated dosing over 2–8 weeks.

Clinical Study: Mostly small Russian clinical reports and case series; modern high-quality RCTs in diverse populations are lacking.

🎯 Mood and motivation (drive)

Evidence Level: Low

• Mechanism: Increased dopaminergic signaling in mesocorticolimbic circuits likely underlies improved motivation/initiative.
• Target: Individuals with apathy or need for short-term motivational enhancement.

Clinical Study: Anecdotal and small clinical observations; rigorous outcome measures and effect sizes are not established.

🎯 Psychomotor performance and reaction time

Evidence Level: Low-to-moderate

• Mechanism: Catecholaminergic augmentation yields faster reaction times and improved coordination in experimental tasks.
• Onset: Acute, within hours.

Clinical Study: Small trials and experimental task data suggest improvements; quantitative effect sizes vary across studies and are not standardized in meta-analyses available in English.

🎯 Neuroprotection / increased stress tolerance

Evidence Level: Low (preclinical)

• Mechanism: Animal models show reduced neuronal vulnerability to hypoxia/ischemia and improved mitochondrial resilience.
• Clinical translation: Human evidence insufficient to claim reliable neuroprotective benefit.

Study: Multiple animal studies show protective effects under hypoxic/ischemic models; human extrapolation remains hypothetical without robust clinical trials.

🎯 Anticonvulsant signal (preclinical)

Evidence Level: Low (preclinical)

• Mechanism: Modulation of excitatory/inhibitory balance may increase seizure threshold in some animal models.
• Clinical use: Not an approved anticonvulsant; avoid use in epilepsy unless under specialist care.

Study: Observations come from animal seizure models; no sufficient human clinical trials support anticonvulsant use.

📊 Current Research (2020–2026)

Between 2020 and 2026 there has been limited expansion of high-quality, English-language randomized clinical trials on phenylpiracetam; research remains dominated by preclinical and small clinical series, many Russian-language.

• Trend: Ongoing small human studies and mechanistic animal work; sporadic translational research but few large RCTs.
• Evidence gap: Lack of reproducible multicenter RCTs with standardized cognitive endpoints and pharmacokinetic profiling in diverse populations.

Actionable item: I can perform a targeted literature retrieval and return a catalog of primary studies with verified PubMed IDs and DOIs (including Russian-English translated sources) if you would like — please confirm and I will proceed.

💊 Optimal Dosage and Usage

Common consumer dosing ranges in practice are 100–300 mg/day, typically divided; some clinical series used up to 400–600 mg/day in divided doses, but higher doses increase adverse effects.

Recommended Daily Dose (NIH/ODS Reference)

• Standard: 100–300 mg/day (typical consumer/nootropic practice).
• Therapeutic range reported: 50–600 mg/day in various small studies/clinical reports (use caution at upper range).
• Note: NIH/ODS and FDA have not issued an official recommended intake for phenylpiracetam; it is not an FDA-approved drug.

Timing

• Best time: Morning or early afternoon to align with pharmacokinetics and avoid sleep disruption.
• With food: Can be taken with or without food; a meal may reduce Cmax and blunt abrupt stimulation.
• Onset: Subjective effects commonly within 30–120 minutes, lasting several hours depending on dose.

Cycle & duration

• Initial trial: 2–4 weeks to evaluate effect and tolerance.
• Common practice: Some users cycle (e.g., 2–6 weeks on, 1–2 weeks off) to limit tolerance; clinical guidance is not standardized.

🤝 Synergies and Combinations

Commonly reported synergistic combinations include choline donors (alpha‑GPC, CDP‑choline) and calming agents (L‑theanine) — these combinations are used to augment cognition and reduce stimulant-like side effects.

• Choline donors: 250–500 mg alpha‑GPC or 250–500 mg CDP‑choline often paired to support acetylcholine synthesis and reduce racetam-associated headaches (anecdotal/practice-based).
• L‑theanine: 100–200 mg co‑administered to smooth stimulation and reduce anxiety.
• Avoid combining with strong prescription stimulants without medical supervision due to additive sympathomimetic effects.

⚠️ Safety and Side Effects

Phenylpiracetam is generally well tolerated short-term; common adverse effects include insomnia, headache, irritability and gastrointestinal upset — frequency estimates are imprecise due to limited population-level data.

Side effect profile (reported)

• Insomnia / sleep disturbance (commonly reported anecdotally)
• Headache (common with racetam use)
• Irritability, anxiety, agitation (dose-related)
• Palpitations / increased heart rate (occasional)
• Gastrointestinal upset (nausea)

Overdose

• Signs: Severe agitation, hypertension, tachycardia, seizures in predisposed individuals, psychotic symptoms (rare).
• Management: Supportive care — discontinue agent, vital sign monitoring, benzodiazepines for severe agitation or seizures, hospital-level care as needed.

💊 Drug Interactions

Phenylpiracetam has important pharmacodynamic interaction risks — especially with stimulants and MAO inhibitors — and renal elimination considerations that mandate caution with nephrotoxic drugs.

⚕️ Stimulants (e.g., methylphenidate, amphetamines, modafinil)

• Interaction: Additive central stimulant and cardiovascular effects.
• Severity: High
• Recommendation: Avoid or use only under specialist supervision with dose reduction and cardiovascular monitoring.

⚕️ MAO inhibitors (selegiline, phenelzine)

• Interaction: Potential potentiation of monoaminergic effects and hypertensive risk.
• Severity: High
• Recommendation: Avoid combination.

⚕️ Antidepressants (SSRIs/SNRIs)

• Interaction: Pharmacodynamic augmentation of neurotransmission; theoretical seizure-threshold risk.
• Severity: Medium
• Recommendation: Monitor closely; consider lower starting dose and specialist input.

⚕️ Antipsychotics (dopamine antagonists)

• Interaction: May reduce phenylpiracetam efficacy; potential for psychiatric destabilization.
• Severity: Medium
• Recommendation: Specialist coordination required for patients with psychotic disorders.

⚕️ Nephrotoxic agents / renal-eliminated drugs

• Interaction: Altered elimination if renal function impaired; avoid concomitant nephrotoxins when possible.
• Severity: Medium
• Recommendation: Monitor renal function and adjust dosing.

🚫 Contraindications

Absolute contraindications include known hypersensitivity to phenylpiracetam or excipients and current MAOI use; relative contraindications include uncontrolled cardiovascular disease, active psychosis, seizure disorder, and severe renal impairment.

Special populations

• Pregnancy/Breastfeeding: Not recommended — insufficient safety data; avoid unless benefits justify risk and under specialist supervision.
• Children: Not routinely recommended; pediatric use only under specialist care with individualized dosing.
• Elderly: Start low and titrate; monitor renal function and comedications.

🔄 Comparison with Alternatives

Compared with piracetam, phenylpiracetam is more lipophilic and typically more potent with stimulant-like effects; compared with prescription wakefulness agents (modafinil), phenylpiracetam lacks comparable regulatory oversight and robust RCT evidence.

✅ Quality Criteria and Product Selection (US Market)

Prefer finished products with third-party testing (CoA), GMP compliance and transparent labeling; avoid bulk powders from unverified vendors.

• Quality markers: Certificate of analysis, third-party testing (HPLC/GC‑MS), GMP manufacturing, heavy metals and microbial testing.
• Useful certifications: NSF, USP Verified (if applicable), ConsumerLab reports.
• Where to buy: Specialty nootropic retailers, compounding pharmacies, larger marketplaces (Amazon, iHerb, Vitacost) — verify CoA before purchase.
• Red flags: No CoA, unverifiable origin, exaggerated medical claims, inconsistent labeling.

📝 Practical Tips

• Start at the low end (50–100 mg) to assess tolerance; titrate carefully to 100–300 mg/day if needed.
• Take in morning/early afternoon to minimize insomnia risk.
• Consider pairing with a choline source (alpha‑GPC 250–500 mg) and/or L‑theanine (100–200 mg) to mitigate headaches/anxiety (anecdotal practice).
• Check athlete anti-doping rules before using; phenylpiracetam may be prohibited in competition.
• Consult a clinician before combining with prescription stimulants, antidepressants, MAOIs, or in renal impairment.

🎯 Conclusion: Who Should Take Phenylpiracetam?

Phenylpiracetam may suit adults seeking short-term improvements in attention, processing speed and reduced perceived fatigue — but benefits are supported mainly by limited clinical series and preclinical data; strong randomized controlled trial evidence is lacking.

• Consider if: You need occasional, short-term cognitive/anti-fatigue support and accept limited evidence and uncertain regulatory status.
• Avoid if: You have uncontrolled cardiovascular disease, active psychosis, seizure disorder, are pregnant/breastfeeding, or are a competitive athlete without confirming doping rules.
• Next step: If you want verified primary-study citations (including Russian clinical reports and any PubMed-indexed trials), request a targeted literature retrieval and I will fetch full citations (PMIDs/DOIs) and translate where needed.

Disclaimer: This article synthesizes available evidence and practice-based dosing from supplier datasheets and clinical reports. Phenylpiracetam is not an FDA-approved drug in the United States; consult your healthcare provider before use.