Melanotan II and PT-141 Stack: Two Melanocortin Drugs, One Receptor Family
Melanotan II and PT-141 both act on melanocortin receptors - what stacking them means, what dosing sources say, side effects and legal status.
The short version
Melanotan II and PT-141 (bremelanotide) are both melanocortin receptor agonists, so combining them doubles up on one receptor family rather than adding a second one. PT-141 is FDA-approved as Vyleesi at a fixed 1.75 mg as needed. Melanotan II has no approved product or dose. Two independent dosing sites describe separating the two doses in time when stacking them. They disagree on whether to reduce the amounts, and neither points to a published study of the pair together.
- Melanotan II and PT-141 both act on melanocortin receptors - stacking doubles up on one family, not two.
- PT-141 is FDA-approved as Vyleesi at a fixed 1.75 mg as needed; Melanotan II has no approved dose.
- Two independent dosing sites describe time-separated doses when stacking the two - not a tested protocol.
- No published study has tested Melanotan II and PT-141 given together, at any dose.
Melanotan II and PT-141 (bremelanotide) are often mentioned together. PT-141 was developed out of melanotan research, and both are melanocortin receptor agonists. That shared mechanism is the key fact about stacking them: the pair is two agonists on overlapping receptors, not two tools working different angles. This page covers what that means, what dosing sources say about combining them, and where the two stand very differently with FDA.
For each compound alone, see the Melanotan guide and the PT-141 guide. For dosing detail, see Melanotan 2 dosage and PT-141 dosage. For Melanotan I (afamelanotide), see Melanotan 1.
Side by side
| PT-141 (bremelanotide) | Melanotan II | |
|---|---|---|
| Approval | FDA-approved, as Vyleesi | Never approved anywhere |
| Approved use | Hypoactive sexual desire disorder, premenopausal women | None |
| Receptor | Melanocortin receptors, mainly MC3R/MC4R | Melanocortin receptors, broadly MC1R/MC3R/MC4R/MC5R |
| Dose with evidence | 1.75 mg subcutaneous, fixed, as needed (FDA label) | No approved dose; 0.01-0.03 mg/kg in one small 1996 trial |
| Route sold today | Prescription autoinjector (Vyleesi) or unverified research vial | Unverified research vial only |
| Human trial data | Phase 2b dose-ranging plus two Phase 3 trials in women; a separate older trial in men | One small Phase I pilot in 3 men |
Both act on melanocortin receptors - stacking doubles up, it does not add a second target
Melanotan II is a broad melanocortin agonist. It is active at MC1R (the receptor most responsible for pigmentation), MC3R and MC4R (appetite and sexual-desire pathways) and MC5R. PT-141 was designed out of that same research family to act on MC3R and MC4R with less MC1R activity. That is why it tans less than Melanotan II.
Running both puts two agonists onto receptors the first is already occupying. It does not combine two separate mechanisms. This site’s protocol builder applies the same “same-target” flag to any two compounds sharing a receptor family. That is a statement about mechanism, not a verdict on whether the combination is dangerous. No published study has measured the combined effect either way.
What dosing sources say about combining them
Two independent dosing sites describe stacking Melanotan II and PT-141 with the two doses kept apart in time. Neither reports a study behind its numbers.
- PeptideWiki’s Melanotan II dosage guide describes a Melanotan II maintenance schedule of 0.5-1 mg once or twice a week, with PT-141 at 1.75 mg as needed. It says not to use the two on the same day, because combining them raises the risk of nausea, flushing and blood pressure changes.
- RealPeptides’ stacking guide independently recommends reduced amounts when the two are combined. It suggests roughly 300-500 mcg of Melanotan II and 0.75-1.25 mg of PT-141, dosed 8-12 hours apart rather than injected together. It also describes running the combination on fewer days per week than either compound alone, to limit how much receptor activity is stacked at once.
The two sources agree that the doses should be separated in time, and both name 500 mcg of Melanotan II. They disagree on whether to cut the amounts. RealPeptides reduces both, while PeptideWiki keeps PT-141 at its labelled 1.75 mg and moves it to a different day. They also differ on the weekly pattern. Neither cites a clinical study of Melanotan II plus PT-141 together, and both frame their guidance as dosing-site practice, not trial evidence.
Melanotan II 10 mg vial (as described for this stack)
| Water added | Concentration | 1 unit = | 300 mcg | 500 mcg | 1 mg |
|---|---|---|---|---|---|
| 1 mL water | 10 mg/mL | 100 mcg | 3 units | 5 units | 10 units |
| 2 mL water | 5 mg/mL | 50 mcg | 6 units | 10 units | 20 units |
| 3 mL water | 3.33 mg/mL | 33.33 mcg | 9 units | 15 units | 30 units |
Units on a U-100 insulin syringe (100 units = 1 mL), to the nearest half unit. 300-500 mcg is RealPeptides' reduced stacking range and 500-1,000 mcg is PeptideWiki's maintenance range (PeptideWiki also names the 10 mg vial); 500 mcg is the amount both name. Neither site is a clinical or regulatory source. PT-141's approved dose is a fixed 1.75 mg from a ready-to-use autoinjector, not a reconstituted vial - see the PT-141 section below.
PT-141’s approved dose does not change when stacked
US legal status - FDA-approved · prescription only
Vyleesi (bremelanotide) is FDA-approved for premenopausal women with acquired, generalised hypoactive sexual desire disorder, at a labelled dose of 1.75 mg subcutaneously as needed. The label describes that single fixed dose used alone; it does not address use alongside Melanotan II or any other melanocortin agonist.
The label sets one dose: 1.75 mg subcutaneously, at least 45 minutes before anticipated sexual activity. Use it no more than once in 24 hours and no more than eight times a month Kingsberg 2019 - Kingsberg SA, Clayton AH, Portman D et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019;134(5):899-908., in the references below. That figure came from a Phase 2b dose-ranging trial in women Althof 2019 - Althof S, Derogatis LR, Greenberg S et al. Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide. J Sex Med. 2019;16(8):1226-1235., in the references below. It was carried unchanged into the two Phase 3 RECONNECT trials supporting approval Kingsberg 2019 - Kingsberg SA, Clayton AH, Portman D et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019;134(5):899-908., in the references below. None of that trial program tested PT-141 alongside Melanotan II.
A separate, older trial tested bremelanotide in men at a 10 mg intranasal dose. That is a different route and a much larger amount than the approved 1.75 mg subcutaneous dose Safarinejad 2008 - Safarinejad MR, Hosseini SY. Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study. J Urol. 2008;179(3):1066-71., in the references below. The journal later published a formal Expression of Concern about that study Safarinejad 2023 - Safarinejad MR, Hosseini SY. Expression of Concern: Salvage of Sildenafil Failures With Bremelanotide: A Randomized, Double-Blind, Placebo Controlled Study. J Urol. 2023., in the references below. Full detail on both is on the PT-141 dosage page.
Melanotan II has no approved dose, in this stack or alone
US legal status - Research use only
Melanotan II has no FDA-approved product and no approved dose. It was nominated to, then withdrawn from, FDA’s Category 2 bulk-substance safety-risk review, and is not eligible for lawful 503A compounding.
AU legal status - Not on the ARTG
Not on the Australian Register of Therapeutic Goods, so the TGA has not assessed it for safety, quality or effectiveness. Goods that are not on the ARTG cannot lawfully be supplied or advertised in Australia except through a specific pathway - the Special Access Scheme, an Authorised Prescriber, a clinical trial, or personal importation.
Regulators reach their own conclusions on their own timelines. Where these two disagree, the difference is the point - not an error.
The entire published human dosing record for Melanotan II is a single 1996 pilot Phase I trial in 3 men. It escalated from 0.01 mg/kg to 0.025-0.03 mg/kg daily on weekdays for two weeks Dorr 1996 - Dorr RT, Lines R, Levine N et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-84., in the references below. That trial did not involve PT-141 or any other melanocortin drug given alongside it. Full detail, including a published case report of toxicity from a single 6 mg overdose, is on the Melanotan 2 dosage page.
Side effects and risks
The Vyleesi label lists these effects:
- Nausea, the most common reaction, affecting roughly 40% of patients.
- Transient increases in blood pressure and decreases in heart rate, which typically resolve within about 12 hours.
- Focal skin hyperpigmentation, which has not been confirmed to resolve in every patient. It is more often reported with darker skin and with more frequent dosing.
The label advises against use in anyone with uncontrolled hypertension or known cardiovascular disease.
Published case literature associates Melanotan II, separately, with three problems:
- Priapism Dreyer 2019 - Dreyer BA, Amer T, Fraser M. Melanotan-induced priapism: a hard-earned tan. BMJ Case Rep. 2019;12(2)., in the references below.
- Discussion of renal infarction Peters 2020 - Peters B, Hadimeri H, Wahlberg R et al. Melanotan II: a possible cause of renal infarction: review of the literature and case report. CEN Case Rep. 2020;9(2):159-161., in the references below.
- A documented case of rhabdomyolysis and acute kidney injury after a single 6 mg overdose Nelson 2012 - Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012;50(10):1169-73., in the references below.
No published source has measured whether nausea, blood pressure change or pigmentation happen more often, or more severely, when the two compounds are used together rather than alone. The two dosing sites above keep the doses apart in time, and one also reduces them, because that question has not been answered.
Is this stack legal?
PT-141 is legal when it is Vyleesi, prescribed by a clinician for its approved indication and used at its labelled dose. That approval does not extend to combining it with Melanotan II or any other unapproved compound. Melanotan II itself has no FDA-approved product in any form and is sold as a research chemical, not a legally marketed drug.
See each compound’s own page for the full jurisdiction-specific detail: Melanotan and PT-141. For how US law treats research-use-only peptides generally, see research peptides and the law.
For where research-labelled peptides are sourced, see this site’s research-access page. It sends readers to a specific research-peptide supplier and discloses that relationship on that page.
Related
- Melanotan: what the published cases show
- PT-141: what the evidence shows
- Melanotan 2 dosage: the common protocol and trial dose
- PT-141 dosage: the approved dose and the older male-trial data
- Dosage calculator
- Peptide side effects
Common questions
What is the usual dose for stacking Melanotan II and PT-141?
Two independent dosing sites describe keeping the two doses apart in time. One describes 0.5-1 mg of Melanotan II once or twice a week as maintenance, with PT-141 at 1.75 mg as needed and never on the same day. The other describes reduced amounts - roughly 300-500 mcg of Melanotan II and 0.75-1.25 mg of PT-141 - dosed 8-12 hours apart. Both name 500 mcg of Melanotan II. Neither figure comes from a study of the combination. Both are dosing-site guidance for a pair that has not been tested together.
Why does it matter that both act on the same receptor family?
Melanotan II activates melanocortin receptors broadly, including MC1R (pigmentation), MC3R and MC4R (appetite and sexual pathways) and MC5R. PT-141 was developed from melanotan research to act on MC3R and MC4R with less MC1R activity. Running both adds a second agonist onto receptors the first is already occupying, not a separate mechanism. The stack builder flags the same logic for any two compounds sharing a target.
Is this stack FDA-approved?
No, not as a combination, and only half of it individually. PT-141 is FDA-approved as Vyleesi, for premenopausal women with hypoactive sexual desire disorder, at its own labelled dose. Melanotan II has no FDA-approved product, no approved indication and no dose set by any regulator. Combining the two is outside Vyleesi's approval, which covers the drug used alone at the labelled dose.
Has Melanotan II plus PT-141 been tested in a study?
I could not locate any published human study that gave Melanotan II and PT-141 together, at any dose. PT-141 (as bremelanotide) has its own Phase 2b and Phase 3 trial data in women, and a smaller older trial in men using a different route. Melanotan II's only published human dosing data is a small 1996 pilot trial. Neither line of research tested the two combined.
What are the side effects of combining Melanotan II and PT-141?
The Vyleesi label lists nausea (most common, affecting roughly 40% of patients), transient increases in blood pressure and decreases in heart rate, and focal skin hyperpigmentation with repeated dosing. Published case reports describe Melanotan II separately with priapism, rhabdomyolysis after an overdose, and a case discussing renal infarction. No published source has measured whether combining the two changes the rate or severity of any of that.
Is Melanotan II legal?
No product containing Melanotan II has FDA approval. It is sold as a research chemical, not legally marketed for human use in the US. See the legal status section below for the jurisdiction-specific detail on each compound.
References (12 sources)
Bibliographic detail is fetched from PubMed, not written by me - so a citation here cannot drift from the paper it names. Study design comes from PubMed's own tags rather than my judgement.
- 1.Dorr RT, Lines R, Levine N et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study. Life Sci. 1996;58(20):1777-84.Clinical trialPMID 8637402
- 2.Nelson ME, Bryant SM, Aks SE. Melanotan II injection resulting in systemic toxicity and rhabdomyolysis. Clin Toxicol (Phila). 2012;50(10):1169-73.Case reportPMID 23121206
- 3.Dreyer BA, Amer T, Fraser M. Melanotan-induced priapism: a hard-earned tan. BMJ Case Rep. 2019;12(2).ReviewPMID 30796078full text
- 4.Peters B, Hadimeri H, Wahlberg R et al. Melanotan II: a possible cause of renal infarction: review of the literature and case report. CEN Case Rep. 2020;9(2):159-161.ReviewPMID 31953620full text
- 5.Kingsberg SA, Clayton AH, Portman D et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019;134(5):899-908.Randomised trialPMID 31599840full text
- 6.Althof S, Derogatis LR, Greenberg S et al. Responder Analyses from a Phase 2b Dose-Ranging Study of Bremelanotide. J Sex Med. 2019;16(8):1226-1235.Randomised trialPMID 31277966
- 7.Safarinejad MR, Hosseini SY. Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study. J Urol. 2008;179(3):1066-71.Randomised trialPMID 18206919
- 8.Safarinejad MR, Hosseini SY. Expression of Concern: Salvage of Sildenafil Failures With Bremelanotide: A Randomized, Double-Blind, Placebo Controlled Study. J Urol. 2023.StudyPMID 36626345
- 9.VYLEESI (bremelanotide) injection - full prescribing information: labelled dose, frequency caps, and the adverse-reaction rates for nausea, blood pressure/heart rate change and focal hyperpigmentation.- DailyMed, National Library of Medicinelabel
- 10.FDA - Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks (Category 2 list and the withdrawn-nominations table, which includes Melanotan II).- US Food and Drug Administrationregulatory
- 11.PeptideWiki’s Melanotan II dosage guide- peptidewiki.coother
- 12.RealPeptides’ stacking guide- realpeptides.coother