(S)-CE-123

Overview

(S)-CE-123 is a non-peptide small molecule belonging to the diphenylmethyl-sulfinyl-thiazole chemotype, structurally related to modafinil. It acts as an atypical, non-releasing dopamine transporter (DAT) inhibitor—blocking dopamine reuptake without triggering amphetamine-like transporter-mediated release. No human clinical data exist; all pharmacology, behavioral, and pharmacokinetic findings are preclinical (rodent in vivo and human-liver-microsome/HEK293-cell in vitro). The compound is not individually named on WADA's current Prohibited List, though modafinil (the parent compound) is a named S6 stimulant; no authoritative WADA ruling specific to CE-123 was found.

Mechanism of Action

(S)-CE-123 is an atypical, non-releasing inhibitor of the dopamine transporter (DAT): it blocks dopamine reuptake by binding DAT without triggering transporter-mediated (amphetamine-like) dopamine release. In vitro studies using HEK293 cells expressing human DAT, NET, and SERT show that (S)-CE-123 inhibits dopamine uptake with EC₅₀ = 2.76 µM, demonstrating ~30-fold selectivity over norepinephrine transporter (NET) and >400-fold selectivity over serotonin transporter (SERT). In vivo microdialysis in rats confirms increased extracellular dopamine in the nucleus accumbens core following systemic administration.

Research Summary

No human data exist for (S)-CE-123. No registered ClinicalTrials.gov trials or DrugBank entries were found, and the primary source explicitly states that no human data are available. All pharmacology and behavioral data are preclinical. In rats, (S)-CE-123 at 24.0 mg/kg i.p. partially reversed tetrabenazine-induced deficits in effort-based lever pressing, increased progressive-ratio responding, and raised extracellular dopamine in the nucleus accumbens core. At 0.3–1.0 mg/kg i.p., CE-123 improved extra-dimensional set-shifting in an attentional task without the impulsivity-increasing effects observed with R-modafinil at 10 mg/kg. Daily dosing improved spatial memory acquisition and retrieval in a hole-board task and ameliorated maternal-separation-induced spatial learning deficits in adolescent rats, with sex-dependent effects. Pharmacokinetic studies in rats and human liver microsomes show that S-CE-123 achieves ~5-fold greater unbound brain penetration (Kp,uu,brain = 0.5) than R-modafinil but is metabolized 9.3-fold faster in human liver microsomes (t₁/₂ 39 min vs. 364 min).

Reported Side Effects

• No human safety data exist
• Abuse liability not fully characterized (authors call for dedicated self-administration studies)
• 9.3-fold faster hepatic metabolism than R-modafinil in human liver microsomes (potential for rapid clearance)
• Sold by gray-market vendors labeled 'not for human or veterinary use'
• WADA status unconfirmed (modafinil parent is a named S6 stimulant)

Compare (S)-CE-123 with Others

Research References

• The Novel Atypical Dopamine Uptake Inhibitor (S)-CE-123 Partially Reverses the Effort-Related Effects of the Dopamine Depleting Agent Tetrabenazine and Increases Progressive Ratio Responding. 2019.
• A Novel Dopamine Transporter Inhibitor CE-123 Improves Cognitive Flexibility and Maintains Impulsivity in Healthy Male Rats. 2017. PMID 29230168.
• A daily single dose of a novel modafinil analogue CE-123 improves memory acquisition and memory retrieval. 2018. PMID 29410048.
• Novel Dopamine Transporter Inhibitor, CE-123, Ameliorates Spatial Memory Deficits Induced by Maternal Separation in Adolescent Rats: Impact of Sex. 2022.

Frequently asked questions

Has (S)-CE-123 been independently lab-tested?

Disclosed Labs has collected 2 Certificates of Analysis (COA) for (S)-CE-123 from 2 independent testing labs. 1 vendor has submitted material for testing. Products average 99.9% tested purity across the corpus. Full testing data is available at https://www.disclosedlabs.com/peptides/ce-123/testing.

How does (S)-CE-123 work?

(S)-CE-123 is an atypical, non-releasing inhibitor of the dopamine transporter (DAT): it blocks dopamine reuptake by binding DAT without triggering transporter-mediated (amphetamine-like) dopamine release. In vitro studies using HEK293 cells expressing human DAT, NET, and SERT show that (S)-CE-123 inhibits dopamine uptake with EC₅₀ = 2.76 µM, demonstrating ~30-fold selectivity over norepinephrine transporter (NET) and >400-fold selectivity over serotonin transporter (SERT). In vivo microdialysis in rats confirms increased extracellular dopamine in the nucleus accumbens core following systemic administration.

What does the research say about (S)-CE-123?

No human data exist for (S)-CE-123. No registered ClinicalTrials.gov trials or DrugBank entries were found, and the primary source explicitly states that no human data are available. All pharmacology and behavioral data are preclinical. In rats, (S)-CE-123 at 24.0 mg/kg i.p. partially reversed tetrabenazine-induced deficits in effort-based lever pressing, increased progressive-ratio responding, and raised extracellular dopamine in the nucleus accumbens core. At 0.3–1.0 mg/kg i.p., CE-123 improved extra-dimensional set-shifting in an attentional task without the impulsivity-increasing effects observed with R-modafinil at 10 mg/kg. Daily dosing improved spatial memory acquisition and retrieval in a hole-board task and ameliorated maternal-separation-induced spatial learning deficits in adolescent rats, with sex-dependent effects. Pharmacokinetic studies in rats and human liver microsomes show that S-CE-123 achieves ~5-fold greater unbound brain penetration (Kp,uu,brain = 0.5) than R-modafinil but is metabolized 9.3-fold faster in human liver microsomes (t₁/₂ 39 min vs. 364 min).