PT-141
A synthetic cyclic heptapeptide derived from the C-terminal hydroxyl variant of Melanotan II. PT-141 acts as a selective agonist at central melanocortin receptors — principally MC3-R and MC4-R — and is studied for its role in neuroendocrine signalling, autonomic arousal pathways, and CNS-mediated physiological responses independent of gonadal hormone activity.
01 Mechanism of Action
PT-141 (bremelanotide) is a cyclic heptapeptide melanocortin receptor agonist. Its primary pharmacological distinction from earlier melanocortin peptides lies in its CNS-centric activity profile: rather than acting peripherally through vascular or hormonal pathways, PT-141 engages melanocortin receptors within the hypothalamus and limbic system to influence autonomic and neuroendocrine output.
The compound binds selectively to MC3-R and MC4-R subtypes, both of which are densely expressed in hypothalamic nuclei involved in energy balance, autonomic tone, and reward circuitry. MC4-R activation in the paraventricular nucleus and medial amygdala has been linked in preclinical models to modulation of dopaminergic projections and downstream physiological arousal responses.
Structurally, PT-141 is the des-hydroxyl metabolite of Melanotan II — it retains the cyclic lactam bridge (Asp–Lys) but carries a free C-terminal hydroxyl group rather than an amide, which confers slightly altered receptor selectivity and metabolic stability compared to its parent compound. The Aib (α-aminoisobutyric acid) at position 8 and D-Phe at position 4 are key pharmacophoric elements for MC receptor engagement.
02 Research Applications
PT-141 has been investigated across a range of preclinical and clinical research contexts. The following application areas reflect published literature and do not constitute guidance for any applied or therapeutic use.
CNS Melanocortin Signalling
PT-141 is a well-characterised pharmacological tool for probing MC3-R and MC4-R function in hypothalamic circuits. Researchers have used it to examine the role of central melanocortin tone in autonomic arousal, dopamine release dynamics, and the interaction between melanocortin and opioid receptor systems in limbic structures.
Hypoactive Sexual Desire Research
The compound has been studied in clinical trials for hypoactive sexual desire disorder (HSDD) in premenopausal women. Phase 3 data (RECONNECT trials) demonstrated statistically significant improvements in satisfying sexual events and desire scores versus placebo. This research pathway led to FDA approval of the 1.75 mg subcutaneous formulation (Vyleesi) in 2019 — the first non-hormonal, CNS-active compound approved for HSDD.
| Trial | Population | Duration | Primary Endpoint | Outcome |
|---|---|---|---|---|
| RECONNECT-1 | Premenopausal women, HSDD | 24 weeks | eDiary SSE count | Significant improvement vs placebo |
| RECONNECT-2 | Premenopausal women, HSDD | 24 weeks | FSDS-DAO desire subscale | Significant improvement vs placebo |
| Phase 2 (NCT00463086) | Mixed, HSDD / ED | 12 weeks | Sexual response endpoints | Dose-dependent responses observed |
SSE = satisfying sexual event; FSDS-DAO = Female Sexual Distress Scale–Desire/Arousal/Orgasm. Data for research reference only.
PT-141 vs. Melanotan II — Structural Comparison
Erectile Function Research (Preclinical & Phase 2)
Early-phase clinical investigation explored PT-141 in men with erectile dysfunction (ED), including subjects non-responsive to PDE5 inhibitors. Phase 2 data demonstrated erection-facilitating effects mediated through central dopaminergic pathways rather than peripheral vasodilation — a mechanistically distinct action from sildenafil and related compounds. This research line was not advanced to Phase 3 for the ED indication.
03 Observed Research Effects
The following effects are derived from published clinical trial data. All information is presented for research reference only.
Commonly Reported Effects (Clinical Trials)
Nausea is the predominant adverse signal in clinical data, reported in approximately 40% of subjects at the 1.75 mg dose. It typically resolves within two hours and is substantially attenuated by co-administration of antiemetic agents in clinical settings. Haemodynamic effects (blood pressure and heart rate changes) are transient, typically resolving within 12 hours post-administration.
Signals Requiring Monitoring in Research Protocols
- Transient hypertension — Clinically meaningful blood pressure elevations (systolic ≥140 mmHg) were observed in a subset of trial participants. The effect is self-limiting but warrants baseline cardiovascular characterisation in any research subject population. Subjects with pre-existing hypertension or cardiac pathology are excluded from clinical protocols.
- Hyperpigmentation — Focal darkening of skin (particularly face, gums, and breast tissue) has been reported with repeated administration. This effect is attributable to off-target MC1-R activity on melanocytes and may be irreversible with prolonged exposure. More pronounced in individuals with higher baseline melanin density.
- Bradycardia — Transient slowing of heart rate has been observed post-injection, likely via autonomic reflex. Cardiac monitoring is indicated in cardiovascular-sensitive research populations.
- Drug absorption interactions — PT-141 slows gastrointestinal transit via melanocortin receptor activity, potentially delaying absorption of orally administered co-compounds. This interaction is relevant in multi-compound research protocols requiring predictable pharmacokinetics.
- Reproductive toxicity (preclinical) — Animal studies identified embryofetal developmental concerns at supratherapeutic doses. Research protocols involving reproductively active animal populations should account for this finding.
04 Contraindication Profile
The following contraindications are established from clinical trial exclusion criteria and post-marketing data for the approved pharmaceutical formulation. They are presented here for completeness of the research literature record.
These contraindications are relevant context for any researcher designing studies involving PT-141 in live animal or human research settings. For purely in-vitro applications, receptor binding assays, and cell-based studies, these clinical parameters do not directly apply but provide useful pharmacological framing.
Drug Interaction Profile
PT-141 has been shown to delay gastric emptying and slow GI motility via central melanocortin mechanisms. In clinical settings this has resulted in reduced peak plasma concentrations (Cmax) and delayed Tmax for orally co-administered drugs including antibiotics, analgesics, and naltrexone. Researchers using PT-141 alongside other compounds in multi-arm in-vivo protocols should account for these pharmacokinetic interactions.
05 Chemical & Physical Profile
06 Reconstitution Reference
The following concentrations are representative of those used in published PT-141 research protocols. All calculations assume a 5 mg lyophilized vial.
| Bacteriostatic Water Added | Resulting Concentration | Volume per 500 µg dose | Doses per Vial |
|---|---|---|---|
| 1.0 mL | 5,000 µg/mL (5 mg/mL) | 0.10 mL (100 µL) | 10 |
| 2.0 mL | 2,500 µg/mL (2.5 mg/mL) | 0.20 mL (200 µL) | 10 |
| 5.0 mL | 1,000 µg/mL (1.0 mg/mL) | 0.50 mL (500 µL) | 10 |
07 Research Literature
Key publications underpinning PT-141's pharmacological characterisation and clinical development. All are accessible via the cited journals or ClinicalTrials.gov.
Order PT-141 · 5 mg Vial
≥99.2% HPLC purity · CoA from Freedom Diagnostics · Cold shipped · Lot 2603