Comparison
Modafinil vs MOTS-c
Side-by-side of Modafinil and MOTS-c. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Modafinil
Modafinil cognitive enhancement profile: wakefulness-promoting agent, 100-200 mg dosing, 12-15 hour half-life, off-label nootropic use, Schedule IV status.
MOTS-c
MOTS-c peptide is a 16-amino-acid mitochondrial-derived peptide. Preclinical signals for insulin sensitivity, exercise capacity, dosage notes.
Effects at a glance
Modafinil
- •FDA approved in 1998 for narcolepsy, with later additions for shift-work sleep disorder and OSA residual sleepiness
- •Schedule IV controlled substance in the US; prescription-only in EU, UK, Australia
- •Increases wakefulness via weak dopamine reuptake inhibition plus histaminergic, noradrenergic, and orexinergic activation
- •Long half-life of 12 to 15 hours requires morning dosing to avoid sleep disruption
- •Modest cognitive enhancement signal in non-sleep-deprived adults at 100 to 200 mg (Battleday meta-review 2015)
- •Substantial CYP3A4 induction reduces hormonal contraceptive efficacy; barrier methods recommended
MOTS-c
- •16-amino-acid peptide encoded in mitochondrial DNA (12S rRNA region); discovered 2015
- •Activates AMPK in skeletal muscle and liver; improves insulin sensitivity in rodent models
- •Circulating endogenous levels decline with age, motivating the longevity-restoration hypothesis
- •CohBar's MOTS-c analog CB4211 discontinued after phase 1b NASH readout did not meet endpoints
- •Anecdotal protocols use 5 to 10 mg subcutaneously 2 to 3 times weekly
- •Not on the WADA Prohibited List as of 2026; future scrutiny likely given exercise-mimetic mechanism
Side-by-side
| Attribute | Modafinil | MOTS-c |
|---|---|---|
| Category | pharmaceutical | peptide |
| Also known as | Provigil, Modalert, Modvigil, diphenylmethylsulfinyl-acetamide | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc |
| Half-life (hr) ↗ | 13 | 0.5 |
| Typical dose (mg) ↗ | 200 | 5 |
| Dosing frequency | daily, morning | 2-3x weekly |
| Routes | oral | subcutaneous |
| Onset (hr) | 1 | 1 |
| Peak (hr) | 3 | 4 |
| Molecular weight | 273.35 | 1880.18 |
| Molecular formula | C15H15NO2S | C82H132N22O25S2 |
| Mechanism | Weak dopamine reuptake inhibition plus downstream activation of histaminergic, noradrenergic, and orexinergic wake-promoting systems. | Mitochondrial-derived peptide that activates AMPK in skeletal muscle and liver, improves insulin sensitivity, and translocates to the nucleus under metabolic stress to modulate nuclear gene expression in retrograde mitochondrial signaling. |
| Legal status | Schedule IV (US); prescription-only globally; not a supplement | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List |
| WADA status | banned | unknown |
| DEA / Rx | Schedule IV | Not scheduled (research chemical) |
| Pregnancy | Not recommended | Insufficient data; not recommended |
| CAS | 68693-11-8 | 1627580-64-6 |
| PubChem CID | 4236 | 139599184 |
| Wikidata | Q422968 | Q24832108 |
Safety profile
Modafinil
Common side effects
- headache
- nausea
- anxiety
- insomnia (with late-day dosing)
- dry mouth
- mild blood pressure elevation
Contraindications
- recent myocardial infarction
- unstable angina
- left ventricular hypertrophy
- significant arrhythmia
- history of Stevens-Johnson syndrome
- psychotic disorders
- pregnancy
- concurrent MAOI use
Interactions
- hormonal contraceptives: CYP3A4 induction reduces contraceptive efficacy; use barrier method(major)
- cyclosporine: reduced cyclosporine levels via CYP3A4 induction(major)
- warfarin: CYP2C9 inhibition raises INR(moderate)
- phenytoin: CYP2C19 inhibition raises phenytoin levels(moderate)
- MAOIs: potential hypertensive reaction(major)
- classical stimulants (amphetamine, methylphenidate): additive cardiovascular and sleep-disruption effects(moderate)
MOTS-c
Common side effects
- injection-site irritation
- transient fatigue
- headache (anecdotal)
Contraindications
- pregnancy
- lactation
- active malignancy (theoretical)
- severe hypoglycemia risk on concurrent insulin or sulfonylurea
Interactions
- insulin: additive insulin sensitization may increase hypoglycemia risk(moderate)
- metformin: both activate AMPK; theoretical additive metabolic effect, no controlled data(minor)
- sulfonylureas: increased hypoglycemia risk via additive insulin sensitization(moderate)
Which Should You Take?
Modafinil comes out ahead for most readers on the criteria we weight: 3 catalogued goals, controlled substance, oral dosing, with a Tier-A outcome catalogued. MOTS-c is the right call when one of the conditionals below applies.
- → If your priority is wakefulness, pick Modafinil.
- → If your priority is focus or working memory, pick Modafinil.
- → If your priority is healthspan extension, pick MOTS-c.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
Edge case: If you cannot self-administer injections, Modafinil is the only oral option in this pair.
Default choice: Modafinil. Wider use case, a Tier-A evidence outcome catalogued, and broader goal coverage. Reach for MOTS-c only if your priority sits squarely in the goals it owns above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Modafinil and MOTS-c?
Modafinil and MOTS-c differ in category (pharmaceutical vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Modafinil or MOTS-c?
Modafinil half-life is 13 hours; MOTS-c half-life is 0.5 hours.
Can you stack Modafinil with MOTS-c?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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