PT-141

Research · PT-141

Overview

PT-141 (bremelanotide) is a synthetic cyclic seven-residue analog of alpha-melanocyte-stimulating hormone (alpha-MSH), closed by a lactam bridge, and is an active metabolite of melanotan II, from which it differs by a C-terminal free acid in place of an amide. It was developed by Palatin Technologies and was approved for clinical use in the United States in 2019. It is used as a reference agonist in research on central melanocortin signaling. Its cyclic structure confers resistance to proteolytic degradation relative to the linear native hormone, supporting its use in in vivo pharmacology studies.

Mechanism of action

Acts as a non-selective agonist at melanocortin receptors, with highest relevance at the melanocortin 4 receptor (MC4R) and activity at MC1R, MC3R, and MC5R. These are Gs-coupled G-protein-coupled receptors that increase intracellular cAMP upon activation. MC4R is expressed in hypothalamic nuclei including the medial preoptic area, where receptor activation is proposed to modulate dopaminergic signaling in circuits governing sexual motivation. Unlike PDE5 inhibitors, its effects are mediated centrally rather than through peripheral vascular nitric oxide-cGMP pathways. Activity at MC1R on melanocytes accounts for reported pigmentation changes.

Key research findings

1. 01

   Preclinical rodent studies characterize MC4R-dependent effects on solicitation and appetitive sexual behaviors, abolished by melanocortin receptor antagonism.

2. 02

   Early clinical studies (2006) characterized effects on subjective sexual response endpoints in premenopausal participants with sexual arousal disorder.

3. 03

   Two phase 3 randomized controlled trials (RECONNECT) characterized desire and distress endpoints, supporting the 2019 regulatory review.

4. 04

   Ambulatory blood pressure studies characterized transient increases in systolic and diastolic pressure, and clinical data document nausea and focal hyperpigmentation as common adverse events.

Published references

• Bremelanotide: First Approval

  Dhillon S et al. — Drugs, 2019 · PMID: 31429064

• An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist

  Diamond LE et al. — J Sex Med, 2006 · PMID: 16839319

The information above is derived from published preclinical and clinical research. It is provided for educational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations.