Comparison
MOTS-c vs PT-141
Side-by-side of MOTS-c and PT-141. 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.
MOTS-c
MOTS-c peptide is a 16-amino-acid mitochondrial-derived peptide. Preclinical signals for insulin sensitivity, exercise capacity, dosage notes.
PT-141
PT-141 peptide (bremelanotide, Vyleesi): MC4R agonist for libido and erectile dysfunction. 1.75 mg subcutaneous, 30 to 60 min onset, 2 to 4 h half-life.
Effects at a glance
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
PT-141
- •Cyclic 7-amino-acid synthetic peptide and melanocortin receptor agonist (MC4R-preferring)
- •FDA approved in 2019 as Vyleesi for hypoactive sexual desire disorder in pre-menopausal women
- •Acts centrally on hypothalamic sexual-desire circuits rather than peripherally on vasculature
- •On-demand dosing: subcutaneous 1.75 mg approximately 45 minutes before sexual activity
- •Common adverse effects: nausea (~40%), flushing, headache, injection-site reactions, hyperpigmentation
- •Off-label male ED use is documented but not FDA approved; mechanism is distinct from PDE5 inhibitors
Side-by-side
| Attribute | MOTS-c | PT-141 |
|---|---|---|
| Category | peptide | peptide |
| Also known as | Mitochondrial Open Reading Frame of the Twelve S rRNA-c, MOTSc | Bremelanotide, Vyleesi |
| Half-life (hr) ↗ | 0.5 | 2.7 |
| Typical dose (mg) ↗ | 5 | 1.75 |
| Dosing frequency | 2-3x weekly | as needed (max once per 24 hours, max 8 per month) |
| Routes | subcutaneous | subcutaneous |
| Onset (hr) | 1 | 0.75 |
| Peak (hr) | 4 | 1.5 |
| Molecular weight | 1880.18 | 1025.18 |
| Molecular formula | C82H132N22O25S2 | C50H68N14O10 |
| Mechanism | 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. | Synthetic agonist of melanocortin receptors with preference for MC4R, expressed in hypothalamic and limbic circuits regulating sexual motivation. Engages central pathways distinct from peripheral PDE5-mediated vasodilation. |
| Legal status | Not FDA approved; research-use-only grey market; not currently on WADA Prohibited List | Prescription only as Vyleesi; FDA-approved 2019 for HSDD in pre-menopausal women. Compounded versions sold off-label for male sexual function are research-use-only grey market. |
| WADA status | unknown | allowed |
| DEA / Rx | Not scheduled (research chemical) | Rx only (not a controlled substance) for the FDA-approved Vyleesi formulation |
| Pregnancy | Insufficient data; not recommended | Not recommended; contraindicated during pregnancy per Vyleesi label |
| CAS | 1627580-64-6 | 189691-06-3 |
| PubChem CID | 139599184 | 9941379 |
| Wikidata | Q24832108 | Q422059 |
Safety profile
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)
PT-141
Common side effects
- nausea (~40%)
- flushing
- headache
- injection-site reactions
- hyperpigmentation (focal, gums, face, breasts)
- transient blood pressure increase (~6 mmHg systolic)
Contraindications
- uncontrolled hypertension
- established cardiovascular disease
- pregnancy
- naltrexone co-administration (reduces opioid efficacy due to MC receptor crosstalk)
Interactions
- naltrexone (oral): bremelanotide reduces oral naltrexone exposure significantly; avoid co-administration(major)
- antihypertensives: transient BP rise after bremelanotide can offset BP control(moderate)
- PDE5 inhibitors (sildenafil, tadalafil): no documented adverse interaction; mechanisms are non-overlapping(minor)
Which Should You Take?
PT-141 comes out ahead for most readers on the criteria we weight: 2 catalogued goals, research-only / gray-market sourcing, with a Tier-A outcome catalogued. MOTS-c is the right call when one of the conditionals below applies.
- → If your priority is healthspan extension, pick MOTS-c.
- → If your priority is metabolic health and glucose control, pick MOTS-c.
- → If your priority is sexual function, pick PT-141.
- → If your priority is libido, pick PT-141.
Edge case: PT-141 is contraindicated in pregnancy; MOTS-c is the safer pick if that applies.
Default choice: PT-141. 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 MOTS-c and PT-141?
MOTS-c and PT-141 differ in category (peptide vs peptide), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, MOTS-c or PT-141?
MOTS-c half-life is 0.5 hours; PT-141 half-life is 2.7 hours.
Can you stack MOTS-c with PT-141?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
Go deeper