PRE-084 Stats & Data
C1CCC(CC1)(C2=CC=CC=C2)C(=O)OCCN3CCOCC3RQHKZUBCUZVZEF-UHFFFAOYSA-NReceptor Profile
Receptor Actions
Measured Affinities
Guide to PHARMACOLOGYMeasured binding and functional data for PRE-084, curated by the IUPHAR/BPS Guide to PHARMACOLOGY. Each row cites the paper it came from. Lower concentrations mean tighter binding — a value in the sub-nanomolar range indicates a very potent interaction.
| Target | Action | Measure | Value | Concentration | Species | Source |
|---|---|---|---|---|---|---|
| sigma non-opioid intracellular receptor 1 SIGMAR1 | Agonist | pIC50 | 7.4 | 39.81 nM | Human | PMID 1658302 |
Reading this. pKi, pEC50 and pIC50 are negative log molar values, so a higher number means a tighter interaction; the concentration column converts them for you. Values from non-human species are laboratory measurements and do not translate directly to human effect. Receptor affinity is not a dose — it describes what a molecule binds, not how much of it is safe to take.
Receptor data from the IUPHAR/BPS Guide to PHARMACOLOGY (v2026.2), licensed CC BY-SA 4.0. Matched to this substance by InChIKey.
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
No controlled human data on tolerance. Anecdotal users report little acute tachyphylaxis but possible subtle blunting with daily use over >1 week; spacing use by 1–2 weeks likely minimizes carryover. Data quality: anecdotal/low.
Harm Reduction
drugs.wikiName hygiene: no credible primary sources link PRE-084 to the alias “Fenclimorate”; retaining that name risks misidentification during procurement or verification. PubChem lists PRE-084 under the cyclohexanecarboxylate/morpholine ester names noted above. PRE-084 is a selective σ1 receptor agonist used as a research ligand; rodent work shows rapid CNS penetration and a plasma half-life near 3.3 h, but human pharmacokinetics remain unknown. σ1 receptor agonism modulates monoaminergic and glutamatergic signaling and can change the behavioural/toxic profile of stimulants; σ1 antagonists (BD1018/BD1063) attenuate several cocaine effects in mice, implying that σ1 agonists could do the opposite. Several SSRIs interact with σ1 (fluvoxamine/fluoxetine/escitalopram as agonists; sertraline with antagonist/inverse agonist properties), making co-use effects unpredictable. Dextromethorphan is itself a σ1 agonist and can interact at σ1 in animal models; combining high-dose DXM with PRE-084 may magnify or alter effects in either direction. Sparse human reports suggest mild mental stimulation, clarity, and occasionally insomnia; schedule daytime trials and avoid late dosing. Because identity/purity vary by vendor, weigh doses on a 0.001 g scale, and adjust for salt form (HCl ≈10–12% heavier than freebase for equivalent molar dose). Avoid inhalation/vaping routes—thermal decomposition profile is unknown for this ester; insufflation can be irritating and may increase bioavailability unpredictably. People with a history of seizures should avoid σ1 agonist stacks; some σ1-active agents (e.g., opipramol) showed proconvulsant effects in a PTZ-kindling mouse model. As a research chemical without established therapeutic window in humans, employ allergy test dosing (e.g., ≤1 mg) and increase only after ≥24 h with no adverse effects. Polysubstance ‘potentiation’ experiments (e.g., with psychedelics or dissociatives) carry poorly characterized risks due to σ1’s broad cellular roles—avoid until single-agent response is well understood.
References
Data Sources
Cited References
- Bluelight: PRE-084 thread (22 mg sublingual report)
- Bluelight: PRE-084 thread (dose-conversion estimate approximately 1.5 mg)
- Drugs-Forum Drug information: PRE-084
- Hong et al., sigma-1 receptor modulation of dopamine transporter (Nature, 2017)
- Hyrskyluoto et al., Sigma-1 receptor agonist PRE084 is protective against mutant huntingtin-induced cell degeneration
- LGC Standards - Chemical structure and IUPAC name for PRE-084
- Marra et al., pharmacokinetics of PRE-084 in mice (half-life approximately 195 minutes)
- Maurice and Su, The Pharmacology of Sigma-1 Receptors
- MedChemExpress: PRE-084 hydrochloride profile
- PubChem: compound entry for PRE-084
- Su et al., Sigma compounds derived from phencyclidine: identification of PRE-084
- Tocris - PRE-084 hydrochloride product sheet
- TripSit: Wiki - PRE-084
- Marra et al., pharmacokinetics of PRE-084 in mice (half-life ≈195 min)
- Reddit: r/researchchemicals – ‘I have PRE-084!’ (user plans 25-30 mg)
- Reddit: r/Nootropics – Discussion of PRE-084 cognitive effects
- Hong et al., σ-1 receptor modulation of dopamine transporter (Nature, 2017)
Additional references
- PubChem compound entry: PRE-084 (structures, identifiers)
- Marra et al. 2020 – PRE-084 as a tool; mouse PK with t1/2 ≈195 min and rapid CNS distribution (PMC)
- Maurice et al. 1994 – PRE-084, a σ-selective PCP derivative; cognition model in mice (haloperidol antagonism)
- Antidepressant-like effect of PRE-084 in mice; σ1 mechanism
- Neuroprotection in neonatal excitotoxicity model with PRE-084
- ALS model: σ1 agonist PRE-084 improves survival and motor function
- σ1 antagonists (BD1018/BD1063) attenuate cocaine toxicity; agonists can worsen it
- SSRI interactions at σ1: fluvoxamine/fluoxetine/escitalopram agonism; sertraline antagonism/inverse agonism
- Sertraline modulates plasticity via σ1; complex antagonist-like effects
- Dextromethorphan/dimemorfan act at σ1; anticonvulsant/neuroprotective effects depend on σ1
- Dextromethorphan’s antidepressant-like effects involve σ1 receptors
- Antitussive activity of σ1 agonists including PRE-084
- Proconvulsant risk: opipramol (σ1-active) in PTZ-kindling; σ1 antagonist prevents full kindling
- Cocaine–σ1 mechanistic link; BD1063 blocks effects (mechanistic study)
- Bluelight PRE-084 discussion thread (anecdotal human reports incl. sublingual ~20–30 mg)