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THN102
Theranexus's now-discontinued fixed-dose combination of modafinil + sub-antiarrhythmic flecainide.
Aliases (4)
Overview
What is THN102?
THN102 is a fixed-dose combination of modafinil and flecainide (a sodium-channel blocker) developed by Theranexus, designed to enhance modafinil's wake-promoting and pro-cognitive effects by modulating neuron-glia coupling. It is in clinical trials for narcolepsy, Parkinson's sleepiness, and other sleep-wake disorders.
Key Benefits
Provides modafinil-level wakefulness with potentially improved cognitive enhancement and mood effects, may reduce excessive daytime sleepiness in narcolepsy and Parkinson's, and aims for better tolerability than higher-dose modafinil monotherapy.
Mechanism of Action
Modafinil promotes wakefulness primarily by inhibiting the dopamine transporter and modulating histaminergic, orexinergic, and noradrenergic systems. Low-dose flecainide, normally an antiarrhythmic, blocks astrocytic connexin hemichannels modulating neuron-glia communication, theoretically amplifying modafinil's cognitive effects without increased dopaminergic burden.
Pharmacokinetics
▸Brand options2 known
StatusInvestigational only — not approved or scheduled. Modafinil component is Schedule IV (US); flecainide component is Rx-only Vaughan-Williams class IC antiarrhythmic (US).
Peptide Interactions
(tautologically — flecainide is the modafinil-amplifier).
would smooth modafinil-component anxiety, no flecainide interaction.
may *reduce* flecainide proarrhythmic risk via membrane stabilization, plausibly synergistic for safety.
neutral, supports cholinergic side of cognition.
SSRIs (especially paroxetine, fluoxetine), bupropion, terbinafine — raise flecainide levels.
Additive negative inotropy.
Amiodarone, sotalol, quinidine — additive proarrhythmia.
Amphetamines, high-dose caffeine — catecholamine surge increases proarrhythmia risk in flecainide-treated patients.
without K+/Mg2+ monitoring — electrolyte shifts unmask flecainide arrhythmia.
sodium channel + cardiac stress overlap is dangerous.
Quality Indicators
Pharmacy-dispensed, intact packaging
Prescription tablets in original sealed packaging from a licensed pharmacy.
Generic vs branded
Generics are usually fine but bioavailability can vary slightly; track if you switch.
Unbranded blister or counterfeit risk
Counterfeit pharmaceuticals are a known issue; verify pharmacy and lot if buying internationally.
What to Expect
- Day 1PK-driven acute peak per administration. Verify dose tolerated.
- Week 1Steady-state reached for most daily-dosed pharma.
- Week 2-4Therapeutic effect established; titration window if needed.
- Long-termPeriodic monitoring per drug class (labs, BP, ECG as applicable).
Side Effects & Safety
THN102 in trials (Parkinson's + sleep deprivation):
- Comparable to or numerically better than modafinil monotherapy in the small studies.
- No ECG conduction effects observed at THN102 doses.
- No motor or non-motor PD symptom worsening in Parkinson's trial.
Modafinil component side effects: See [modafinil.md] — headache, anxiety, insomnia, rare SJS/DRESS. All apply unchanged.
Flecainide component — REAL CARDIAC RISKS at antiarrhythmic doses (NOT THN102 doses, but worth knowing because dose escalation errors can be fatal):
- CAST trial (1989-1992): Class IC antiarrhythmics (flecainide, encainide) in patients with structural heart disease and ventricular arrhythmias post-MI showed 2.5x higher mortality than placebo. Flecainide was withdrawn from this indication. This is one of cardiology's foundational trials and shaped the entire class warning.
- Proarrhythmia risk: Flecainide can cause new ventricular arrhythmias (incessant VT, torsades-like) especially in patients with: structural heart disease, prior MI, LVH, ischemia, congestive heart failure, or electrolyte disturbances (low K+, low Mg2+).
- Conduction effects: PR prolongation, QRS widening (≥25% increase is a danger signal), bradycardia.
- Negative inotropy: Reduces cardiac contractility — risky in heart failure.
- CYP2D6 metabolism: Flecainide is primarily metabolized by CYP2D6. CYP2D6 poor metabolizers (~7-10% of Caucasians, including the user's ancestry) have ~40-50% higher flecainide exposure — potentially shifting THN102 sub-antiarrhythmic doses toward arrhythmogenic ranges. Modafinil's mild CYP2C19 inhibition further complicates this. Pharmacogenomic blocker for any DIY attempt — the user's CYP2D6 status is unknown until June 2026 23andMe interpretation.
- Drug interactions: Flecainide levels increased by amiodarone, paroxetine, fluoxetine, quinidine, ritonavir, terbinafine. Decreased by CYP2D6 inducers. Beta-blockers + flecainide = additive negative inotropy.
Specific to the user profile:
- 20yo with no known cardiac history → low baseline arrhythmia risk.
- No structural heart disease known but never had an ECG — silent LQTS, Brugada, ARVC, etc., are rare but exist and are exactly what flecainide unmasks fatally.
- High-cardio MMA training → catecholamine surges + possible electrolyte shifts post-training → exactly the conditions where flecainide is most dangerous.
- CYP2D6 status unknown.
Specific watch periods (academic — would matter if pursued)
- Baseline 12-lead ECG mandatory.
- ECG at 1 week and 4 weeks on therapy (PR, QRS, QT intervals).
- Trough flecainide level if available (target <0.2-1.0 µg/mL, well below antiarrhythmic 0.4-1.0 µg/mL therapeutic range).
- Electrolytes (K, Mg) at baseline and any symptoms.
- Stop drug + ECG immediately for: palpitations, syncope, near-syncope, new dyspnea.
References
Sauvet et al. 2019 — Br J Clin Pharmacol — THN102 sleep deprivation Phase 1/2
primary efficacy trial in 20 healthy men, military funding, 40-hr deprivation crossover.
View StudyCorvol et al. 2022 — Movement Disorders 37(2):410-415, doi:10.1002/mds.28840 — THN 102 Parkinson's Phase 2a
n=75 PD patients, ESS primary endpoint, 200/2 met vs placebo.
View StudyTheranexus narcolepsy Phase 2 preliminary results press release
n=48, 300 mg modafinil + 3 or 27 mg flecainide, primary endpoint not met.
View StudyDuchêne et al. 2016 — Cortico-amygdala-striatal activation by modafinil/flecainide combination
preclinical fMRI rationale for THN102.
View StudyBjorness & Greene 2016 — Sleep — Glial gap junctions boost modafinil action commentary
astrocyte gap junction mechanism synthesis.
View StudyLiu et al. 2013 — Modafinil enhances gap junctional communication in cortical astrocytes
original Cx30 modafinil interaction.
View StudyNCT02821715 — Flecainide and THN102 in Narcolepsy clinical trial registry
narcolepsy Phase 2 protocol of record.
View StudyTheranexus 2021 full-year results + strategic shift to rare diseases
official company pivot announcement.
View StudyTheranexus Phase II Parkinson's success press release
March 2020 Parkinson's positive announcement.
View StudyTHX Pharma Batten-1 pipeline page (current)
confirms current Batten-1-only focus, no THN102 listing.
View StudyLARVOL DELTA — flecainide/modafinil (THN102) status tracker
third-party tracker confirming program discontinuation.
View StudyCAST trial NEJM 1991 — flecainide post-MI mortality
foundational class IC safety reference (background, not THN102-specific).
View StudyNeurologyLive coverage — THN102 Parkinson's safety + efficacy
clinician-facing summary of Corvol 2022 data.
View StudyHow was your experience with this compound?
Anonymous · one vote per session · results below at 5+ votes.
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