PR Peptides Research

Cellular Peptide · Checked

PT-141 Spray

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PT-141 Spray product vial
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Methodology

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Cellular Peptide

About PT-141 Spray

Acetate salt

Some suppliers list the acetate form, C52H72N14O12 — the free peptide plus one equivalent of acetic acid. This is a different figure for the same compound in salt form, not a competing value for the free peptide.

Relationship to Melanotan II

PT-141 differs from Melanotan II at exactly one position: the C-terminus.

Melanotan II Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-NH2 C50H69N15O9 1024.18 g/mol

PT-141 Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH C50H68N14O10 1025.16 g/mol

The seven residues, the acetyl cap, and the Asp–Lys lactam bridge are identical. PT-141 carries a free carboxylic acid where Melanotan II carries a carboxamide. Converting the amide to the acid removes one nitrogen and one hydrogen and adds one oxygen — a net difference of approximately 0.98 Da.

That single change is the entire structural distinction, and it is why PT-141 is described as the deamidated active metabolite of Melanotan II. Bremelanotide was identified during Melanotan II research when investigators observed that the erectile and arousal effects tracked with the metabolite rather than the parent compound. Palatin Technologies then developed it specifically for that activity.

Practical consequence: Melanotan II has never been submitted for regulatory approval anywhere, while PT-141 completed a full Phase 3 programme and holds FDA approval. Two compounds one oxygen apart, with entirely different regulatory standing.

Receptor pharmacology

PT-141 is a melanocortin receptor agonist. The receptors emphasised in the sexual-function literature are MC3R and MC4R, with MC4R the primary target discussed in relation to central arousal pathways.

Mechanism as described in the literature

Activation of melanocortin receptors in the central nervous system, particularly within the hypothalamus, initiates neural signalling associated with sexual desire and arousal. The compound acts on the central pathway rather than on peripheral vasculature.

Contrast with PDE5 inhibitors

This distinction is the defining feature of the compound and the reason it occupies a separate therapeutic category.

PDE5 inhibitors (sildenafil, tadalafil)

Act peripherally on vascular smooth muscle to permit erection.

Address the mechanics of the response.

PT-141

Acts centrally on melanocortin receptors to influence desire and arousal. Addresses the initiating signal rather than the mechanics.

The two target different stages of the sexual response cycle, which is why PT-141 has been studied in patients who respond inadequately to PDE5 inhibitors, and why co-administration has been examined.

Pharmacokinetics

Peak plasma concentration reported at approximately 30 minutes after administration. Elimination half-life reported in the range of 2.5 to 3 hours.

RECONNECT (Phase 3)

Two randomized, double-blind, placebo-controlled trials in premenopausal women with acquired, generalized hypoactive sexual desire disorder. Subcutaneous bremelanotide at 1.75 mg, taken on demand, produced statistically significant improvements in sexual desire and reductions in associated distress relative to placebo.

These trials formed the basis of the FDA approval.

(Kingsberg et al., Obstetrics & Gynecology, 2019)

Female sexual arousal disorder — earlier work A study in premenopausal women with sexual arousal disorder examined subjective sexual response following bremelanotide administration.

(Diamond et al., Journal of Sexual Medicine, 2006)

Male erectile dysfunction — investigational

Subcutaneous administration was evaluated in healthy male subjects and in patients with inadequate response to sildenafil, with erectile responses reported at doses of 1 mg and above and onset within approximately 30 minutes.

(Rosen et al., International Journal of Impotence Research, 2004)

Intranasal administration was evaluated in healthy males and patients with mild-to-moderate erectile dysfunction.

(Diamond et al., International Journal of Impotence Research, 2004)

Co-administration of low-dose intranasal bremelanotide with sildenafil produced an enhanced erectile response relative to sildenafil alone.

(Diamond et al., Urology, 2005)

Male use is not an approved indication. This body of work is investigational.

Body weight and appetite — exploratory

As an MC4R agonist, bremelanotide has been examined for effects on satiety and energy intake. Two Phase 1 randomized controlled trials in obese women reported reductions in body weight of up to 1.7 kg and in daily caloric intake of approximately 400 kcal/day relative to placebo.

(Spana et al., Diabetes Obesity & Metabolism, 2022)

Safety profile as reported

Most frequent adverse event is nausea, followed by flushing, injection-site reactions, and headache. A transient increase in blood pressure with a corresponding decrease in heart rate occurs following dosing. The approved product is not recommended for individuals with uncontrolled hypertension or established cardiovascular disease.

Regulatory status

Bremelanotide is FDA-approved as Vyleesi, granted June 21, 2019, for acquired, generalized hypoactive sexual desire disorder in premenopausal women. Developed by Palatin Technologies; commercialised by AMAG Pharmaceuticals.

The approved product is a subcutaneous auto-injector, taken on demand at least 45 minutes before anticipated activity, with a defined maximum dosing frequency specified in the labelling.

The approval is specific to that indication and population. Use in men, and use for erectile dysfunction, is not approved.

Material supplied for laboratory use is a research chemical, not the approved pharmaceutical product. It is not a drug, food, cosmetic, or dietary supplement as supplied, has not been evaluated by the FDA in that form, and is not intended for human or veterinary use.

Structure cyclic 7-residue cyclic 7-residue linear lactam, C-term lactam, C-term 13-residue acid amide CAS 189691-06-3 121062-08-6 75921-69-6 Formula C50H68N14O10 C50H69N15O9 C78H111N21O19 Molecular weight 1025.16 g/mol 1024.18 g/mol 1646.87 g/mol Receptor emphasis MC3R / MC4R non-selective MC1R-preferring central arousal MC1/3/4/5R Regulatory status FDA approved 2019 never submitted FDA and EMA anywhere approved 2019 Approved use HSDD in none erythropoietic premenopausal protoporphyria women

All three derive from α-MSH research at the University of Arizona. PT-141 and Melanotan II differ by a single oxygen atom; Melanotan I is a structurally distinct linear peptide. Literature on one does not transfer to the others.

Reference chemistry

Specifications

PT-141 specifications
AttributeValue
Molecular formulaC50H68N14O10
Molecular weight1025.16 g/mol
CAS Number189691-06-3
PubChem CID9941379 ↗
Residue count7
Structure classcyclic heptapeptide, lactam-bridged
SequenceAc-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH
IUPAC condensedAc-Nle-Asp(1)-His-D-Phe-Arg-Trp-Lys(1)-OH
Cyclizationside-chain lactam bridge, Asp–Lys
INNbremelanotide
Trade nameVyleesi
Cited sources

Peer-reviewed literature

[1]
Molinoff PB, Shadiack AM, Earle D, et al. PT-141: a melanocortin agonist for the treatment of sexual dysfunction
Ann N Y Acad Sci. 2003;994:96-102
View source ↗
[2]
Diamond LE, Earle DC, Heiman JR, et al. An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist
J Sex Med. 2006;3(4):628-38
View source ↗
[3]
Rosen RC, Diamond LE, Earle DC, et al. Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra
Int J Impot Res. 2004;16:135-42
Citation only
[4]
Diamond LE, Earle DC, Rosen RC, et al. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction
Int J Impot Res. 2004;16:51-9
Citation only
[5]
Diamond LE, Earle DC, Garcia WD, Spana C. Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response
Urology. 2005;65(4):755-9
Citation only
[6]
Edinoff AN, Sanders NM, Lewis KB, et al. Bremelanotide for treatment of female hypoactive sexual desire
Neurol Int. 2022;14(1):75-88. PMCID PMC8788464
Citation only
[7]
Kim S, Cho MC, Cho SY, et al. Novel emerging therapies for erectile dysfunction
World J Mens Health. 2020;39(1):48-64. PMCID PMC7752520
Citation only
[8]
Spana C, Jordan R, Fischkoff S. Effect of bremelanotide on body weight of obese women: data from two phase 1 randomized controlled trials
Diabetes Obes Metab. 2022;24(6):1084-93. PMCID PMC9314948
Citation only
[9]
FDA. Vyleesi (bremelanotide) prescribing information. 2019
Citation only
[10]
FDA. Press announcement: FDA approves new treatment for hypoactive sexual desire disorder in premenopausal women
June 21, 2019
Citation only
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