RGPU-95
p-Chlorophenylpiracetam · para-Chlorophenylpiracetam · 4-Chlorophenylpiracetam · p-Cl-Phenylpiracetam · N-carbamoylmethyl-4-para-chlorophenyl-2-pyrrolidone
Last updated
At a glance
Overview
What RGPU-95 Actually Is#
RGPU-95 is the para-chloro analog of phenylpiracetam — a single chlorine atom added to the aromatic ring of fenotropil, and a 5–10× potency multiplier as the result. The compound came out of the Volgograd / Herzen State Pedagogical University program in Russia and was first characterised in print by Tiurenkov and colleagues in 2010. In the behavioural assays they ran, RGPU-95 outperformed fenotropil on anxiety endpoints and matched imipramine on antidepressant endpoints, which is what put it on the radar of the nootropics community in the first place.
"The anxiolytic effect of RGPU-95 was significantly higher than that of Fenotropil in the elevated plus maze and Vogel conflict tests, while its antidepressant activity in the Porsolt test was comparable to imipramine and superior to Fenotropil." — Tiurenkov et al., Eksperimental'naia i Klinicheskaia Farmakologiia (2010)
In practice, users describe it as phenylpiracetam without the jitter — the same cognitive sharpening and eugeroic drive, but with a more pronounced mood-lift and anxiolytic edge and less of the over-stimulated, amphetamine-lite feel. That makes it interesting for cognitive-push days, on-cycle "tren brain" recovery, and pulsed mood-leaning protocols where a flatter affective profile is the goal. The trade-off is the evidence base: no human PK, no clinical trials, and a tolerance curve that flattens fast with daily administration.
The sections below cover the inferred mechanism, the 5–10× potency-adjusted dose ladder against phenylpiracetam, the pulsed cycling structure the community has converged on, choline stacking, the stacks that pair well with it (aniracetam, L-theanine, AAS cognition support), and the side-effect and contraindication profile — including why drug-tested athletes should treat this as banned by default.
How RGPU-95 works
RGPU-95 is the para-chloro analog of phenylpiracetam — a single chlorine atom added to the phenyl ring of the parent fenotropil molecule. That structural tweak increases lipophilicity, sharpens blood-brain-barrier penetration, and shifts the behavioural profile away from phenylpiracetam's eugeroic / stimulant edge and toward a more pronounced anxiolytic and antidepressant signature. No dedicated receptor-binding panel has been published for RGPU-95 itself; mechanism is inferred from (a) the comparative behavioural pharmacology in rats and (b) the well-characterised parent compound.
Dopaminergic and Sigma-1 Modulation#
Like phenylpiracetam, RGPU-95 is thought to act as a weak dopamine reuptake inhibitor with sigma-1 agonism and upregulation of D2/D3 receptor density. This is the axis responsible for the drive, focus, and mood-lift effects experienced acutely. The p-chloro substitution appears to amplify activity at this axis on a per-milligram basis, which is why a 25 mg oral dose of RGPU-95 is functionally comparable to ~200 mg of phenylpiracetam in community reports. For the on-cycle user dealing with "tren brain" or AAS-related anhedonia, this is the mechanism that does the practical work — restoring cognitive sharpness and motivation without adding stimulant load on top of an already-elevated resting heart rate.
Anxiolytic and Antidepressant Activity#
This is where RGPU-95 separates itself from the parent compound. The Tiurenkov et al. 2010 study compared RGPU-95 against fenotropil in male and female Wistar rats across the elevated plus maze, Vogel conflict, and Porsolt forced-swim paradigms.
"The anxiolytic effect of RGPU-95 was significantly higher than that of Fenotropil in the elevated plus maze and Vogel conflict tests, while its antidepressant activity in the Porsolt test was comparable to imipramine and superior to Fenotropil." — Tiurenkov IN et al., Eksperimental'naia i Klinicheskaia Farmakologiia, 2010
The mechanism is not fully resolved but likely involves a combination of GABAergic modulation (a class effect of the pyrrolidone scaffold), serotonergic engagement (implied by imipramine-comparable performance in the Porsolt test), and the dopaminergic activity noted above. Practically, this is the reason RGPU-95 reads as "phenylpiracetam without the jitter" — the mood-lift and anxiety reduction arrive without the wired, over-stimulated edge that limits phenylpiracetam's tolerability in many users.
Cholinergic Facilitation (Racetam Class Effect)#
As a racetam, RGPU-95 facilitates acetylcholine signalling — likely through modulation of nicotinic and muscarinic receptors and enhanced ACh release at the synapse. This is the substrate for the memory and learning effects shared across the racetam family. It is also why a choline source (alpha-GPC 300 mg or CDP-choline 250 mg) is near-universally co-administered. Without it, the racetam-class headache emerges within 4–6 hours as endogenous acetylcholine stores are depleted by sustained cholinergic drive. The headache is fully preventable, not a deal-breaker — but it is the most common reason a first RGPU-95 administration goes poorly.
Glutamatergic and Neuroprotective Activity#
Phenylpiracetam modulates NMDA and AMPA glutamate receptor subtypes and exhibits antihypoxic, neuroprotective behaviour characteristic of the GABA-derived pyrrolidones. RGPU-95 is presumed to share this profile.
"Phenylpiracetam is rapidly and almost completely absorbed after oral administration and demonstrates CNS stimulant and neuroprotective effects through modulation of various neurotransmitter systems." — Malykh AG, Sadaie MR, Drugs, 2010
For the recreational user, this axis matters less acutely than dopaminergic or anxiolytic activity, but it underwrites the broader "feels clean, doesn't burn you out" subjective profile and supports the case for RGPU-95 over harder stimulants in users who are already running AAS-induced cardiovascular load.
Sex-Dependent Response#
A distinctive and reproducible finding in the published behavioural work is that male animals respond more strongly than female animals.
"Male rats were found to be more sensitive to the effects of RGPU-95 compared with females, demonstrating a pronounced reduction in anxiety and depressive behaviors at doses where Fenotropil produced weaker responses." — Tiurenkov IN et al., ResearchGate full-text mirror, 2010
The molecular basis is not established — candidate explanations include sex-differential expression of D2/D3 receptors, sigma-1 binding sites, or steroid-modulated GABAergic tone. Whether the differential translates to humans is unknown. The practical implication is that female subjects should titrate conservatively from the low end of the dose range (5 mg) rather than assuming equivalence to the male-derived community standard.
Net Pharmacological Profile#
What the receptor pharmacology adds up to in practice: a phenylpiracetam-like cognitive and eugeroic foundation, with the dopaminergic and stimulant edges blunted and the anxiolytic / antidepressant axes amplified. The 5–10× potency multiplier over phenylpiracetam holds across most behavioural endpoints, which is why dosing anchors at 15–25 mg rather than 100–200 mg. For the looksmaxxing or on-cycle user, the practical positioning is a cognition and mood tool, not a stimulant — administered as-needed, paired with choline, and pulsed rather than run daily to preserve sensitivity.
Protocol
| Level | Dose | Frequency | Notes |
|---|---|---|---|
| Low | 5–10 mg | As needed | Documented entry-level range |
| Mid | 15–25 mg | As needed | Most commonly studied range |
| High | 30–50 mg | As needed | Pulsed / acute use on cognitively demanding days. Tolerance develops within 5–10 days of consecutive administration — community practice is 2–4 dose days per week, or short 5–10 day blocks followed by an equivalent off-period. Avoid dosing past mid-afternoon to preserve sleep. |
Cycle length & outcomes
Documented cycle
1–2 weeks
Plateau after
2 wks
Cycle Structure#
RGPU-95 is dosed acutely, not cyclically in the AAS sense. The dominant variable is tolerance, which develops within 5–10 days of consecutive administration — a class effect inherited from phenylpiracetam. Protocols are built around pulsed use on cognitively demanding days, or short 5–10 day blocks followed by an equivalent off-period to restore sensitivity.
There is no loading phase. Onset is under 60 minutes orally, peak effect lands at roughly 1 hour, and the active window runs 5–8 hours. No taper is required on discontinuation — RGPU-95 does not act on the HPTA, has no withdrawal syndrome, and is cleared within a day.
Dose Ladder by Goal#
| Goal | Cycle Structure | Dose |
|---|---|---|
| First exposure / titration | Single day, AM | 5–10mg |
| Cognitive push / deadline day | As-needed, 2–4 days/week | 15–25mg |
| Anxiolytic / mood pulse | 5–7 consecutive days, then equal off-period | 10–20mg AM |
| On-cycle "tren brain" support | 2–4 days/week, layered on AAS protocol | 10–20mg AM |
| Pre-training cognitive/eugeroic | Acute, 45–60 min pre-session | 20–30mg |
| Advanced sustained productivity | 5–10 day block, then equal off-period | 30–50mg, occasionally split BID |
The 25mg single dose is the most-cited community anchor, derived from a 10× potency scaling against a 250mg phenylpiracetam reference. Subjects new to the racetam class titrate from 5mg — community reports describe noticeable effects as low as 1–5mg, and overshooting on the first administration produces the same anxiety-tachycardia-insomnia profile that defines a phenylpiracetam overshoot.
Tolerance and Pulsing#
Daily administration flattens the cognitive effect inside 1–2 weeks. The two protocols that survive in community practice:
- Intermittent (preferred): dose 2–4 days per week, never on consecutive days where possible. Preserves sensitivity indefinitely.
- Short blocks: 5–10 consecutive days for a defined output window (a competition prep cognitive push, a deadline sprint, a contest peak week), followed by an equivalent off-period before the next block.
Maximum useful continuous exposure is roughly 2 weeks; beyond that, the dose-response curve has flattened and the off-period is non-negotiable.
Timing and Sleep#
The last administration of the day stops at mid-afternoon. The parent compound is notorious for sleep disruption when dosed late, and RGPU-95's longer subjective duration (5–8 hours vs. phenylpiracetam's 4–6) makes that window stricter, not looser. Split-dose protocols (e.g. 25mg AM + 25mg early afternoon) are documented for advanced users but require an early second dose — no later than 1–2pm for most subjects.
Onset and Expectations#
- Acute effects: noticeable inside 45–60 minutes orally. Sublingual administration of the liquid presentation in ethanol/PG vehicle is faster but not better-characterised pharmacokinetically.
- Mood / anxiolytic signal: present from the first dose in responders, sharpens over a 3–5 day pulse.
- Cognitive effects: acute on each dose day; do not "accumulate" the way classical racetams (piracetam, aniracetam) do over weeks.
- Choline cofactor: 300mg alpha-GPC or 250mg CDP-choline co-administered with every dose. Without it, the 4–6 hour post-peak headache is the most common complaint and the easiest to avoid.
Bloodwork and Monitoring#
No compound-specific markers are established for RGPU-95 — there are no human clinical trials and no chronic toxicology data. Standard monitoring for users layering it onto an AAS or stimulant base:
- Resting blood pressure and heart rate: weekly during active blocks, especially when stacked on AAS-driven hypertension or other stimulants. The phenylpiracetam-class cardiovascular load is real even if subjectively mild.
- CBC / CMP: quarterly for users administering RGPU-95 routinely as part of a broader stack.
- Sleep tracking: subjective or wearable-based. The first compound-attributable side effect to appear is almost always sleep latency or fragmentation; catching it early flags either an over-late dose or an over-frequent administration pattern.
No hormonal panel applies — RGPU-95 is not androgenic, not estrogenic, not HPTA-suppressive, and requires no PCT.
Discontinuation#
Stop on the planned end date. No taper, no rebound, no recovery protocol. The off-period exists to restore receptor sensitivity, not to recover endogenous function. Subjects returning to baseline cognition within 24–48 hours of the final dose is the expected pattern; subjects reporting protracted "flatness" beyond that are usually describing the contrast between an active block and unmedicated baseline, not a withdrawal state.
Risks & mistakes
Common (most users)#
- Insomnia and sleep disruption if administered past mid-afternoon. A class effect of the phenylpiracetam family. Cap dosing at noon; subjects who run a second dose keep it before 2 PM.
- Headache from acetylcholine depletion when administered without a cholinergic cofactor. Co-administration of alpha-GPC 300mg or CDP-choline 250mg alongside RGPU-95 pre-empts this almost entirely.
- Rapid tolerance with consecutive-day administration — cognitive lift flattens within 5–10 days. Pulsed protocols (2–4 days per week, or 5–10 day blocks followed by an equivalent washout) restore sensitivity.
- Mild jitter or wired feeling at the upper end of the beginner range in stimulant-sensitive subjects. Stack 200mg L-theanine, or drop the dose to 5mg for the next exposure.
- Appetite suppression in some users, mirroring the parent. Front-load calories earlier in the day rather than skipping meals.
Uncommon (dose-dependent or individual)#
- Tachycardia and elevated resting heart rate at 30–50mg, particularly when stacked with caffeine or layered onto an AAS protocol where cardiovascular load is already elevated. Resting BP and HR should be tracked; back off the dose or drop the caffeine stack first.
- Anxiety paradox — although RGPU-95 was characterised as more anxiolytic than fenotropil in the elevated plus maze and Vogel conflict tests, individual response varies and a minority report the opposite at higher doses. Reduce to 10–15mg and reassess.
- Yawning, mild dissociation, and afterglow-type residual effects at ≥30mg, consistent with the broader receptor activity reported above 0.2 mg/kg in unpublished animal characterisation. Not dangerous, but flagging the protocol is running rich.
- Flat / disappointing response in female subjects — the only published behavioural study found substantially weaker anxiolytic and antidepressant effects in female Wistar rats:
"Male rats were found to be more sensitive to the effects of RGPU-95 compared with females, demonstrating a pronounced reduction in anxiety and depressive behaviors at doses where Fenotropil produced weaker responses." — Tiurenkov et al., 2010
Whether this translates to humans is unknown; conservative titration from 5mg is the sensible default.
- Bloodwork to spot-check on extended pulsed use: resting blood pressure, CBC, CMP. No compound-specific marker exists.
Rare but serious#
- Hypertensive episodes when stacked onto untreated hypertension or onto stimulant-loaded protocols (high-dose caffeine, ephedrine, AAS-induced HTN). Warning signs: persistent headache, visual disturbance, resting BP >150/95. Discontinue.
- Serotonergic / dopaminergic interactions — the antidepressant signal in animal models plus the inferred dopaminergic activity make co-administration with MAOIs, high-dose SSRIs, SNRIs, or tramadol mechanistically unwise. Warning signs of serotonin excess (agitation, hyperreflexia, sweating, tremor) warrant immediate discontinuation.
- Unknown chronic toxicity. No human safety data exist beyond preclinical rat work and community self-report. Chronic daily administration beyond the documented 1–2 week window is uncharted territory.
Hard contraindications#
- Untreated hypertension. Stimulant-class cardiovascular load is plausible given the parent's profile; the protocol does not get layered onto uncontrolled BP.
- MAOI co-administration. Mechanistically incompatible.
- Drug-tested sport. Phenylpiracetam is on the WADA Prohibited List under S6 stimulants. RGPU-95 is the para-chloro analog and will not survive scrutiny under the same class designation. Tested athletes treat it as banned by default.
- Severe insomnia or unmanaged sleep disorders. The compound will make these worse, not better.
- Stacking with other CNS stimulants (amphetamines, high-dose caffeine + ephedrine combinations, modafinil at full dose). Pick one stimulant axis per protocol.
Gender-specific considerations and ancillary notes#
The published animal data (Tiurenkov et al. 2010, PMID 21254591) show a meaningfully weaker response in female subjects on both anxiety and depression endpoints. Female users in the community generally start at 5mg and titrate slowly; expectations should be calibrated against the possibility that the effect is smaller than the male-derived community reports suggest.
No PCT, no HPTA suppression, no estrogen management — RGPU-95 is not a hormonal compound and standard AAS ancillary considerations do not apply. The only "ancillary" that matters is the choline cofactor (alpha-GPC 300mg or CDP-choline 250mg), which is near-universal in documented protocols and effectively eliminates the racetam-class headache. Pulsed administration with deliberate off-days is the single most important practice for keeping the compound effective and well-tolerated over time.
FAQ — RGPU-95
Research & citations
5 studies cited on this page.
Conclusion
RGPU-95 is a high-potency phenylpiracetam analog dialed in for mood, focus, and cognitive drive, with a unique anxiolytic edge not seen in the parent compound. Protocols in the community consistently emphasize conservative dosing, choline support, and pulsed cycles to avoid tolerance.
Key takeaways:
- Typical dose: 10–25 mg orally, as-needed for cognitive or mood-demanding days
- Cycle structure: 2–4 administration days per week, or up to 10 consecutive days with a matching off-period to prevent tolerance
- Always co-administer a choline source (alpha-GPC 300 mg or CDP-choline 250 mg) to mitigate racetam-class headaches
- Stacks well with L-theanine, low-dose caffeine, or aniracetam for cognitive and mood synergy
- Superior anxiolytic and antidepressant activity versus phenylpiracetam in animal studies (Tiurenkov 2010)
- Avoid dosing late in the day to protect sleep; not for those with untreated hypertension or on other stimulants
For research targeting acute cognitive enhancement with less jitters and more mood elevation than the classic racetams, RGPU-95 is a strong contender—especially when run with discipline on dose, cofactor, and break structure.