PT-141 — Published Research

PT-141 is an agonist at melanocortin-4 receptors (MC4R), which are G protein-coupled receptors expressed in hypothalamic nuclei, limbic structures, and spinal cord. MC4R couples primarily to Gαs, activating adenylyl cyclase and increasing cAMP. In the paraventricular nucleus of the hypothalamus, MC4R activation modulates autonomic outflow. Research examines MC4R signaling cascades through downstream oxytocinergic pathways in experimental models.

Wikberg JE, Mutulis F. “Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction.” Nat Rev Drug Discov. 2008. PubMed

Bremelanotide is a cyclic lactam analog derived from Melanotan II through C-terminal amide-to-acid modification. In competitive binding assays, bremelanotide demonstrates agonist activity at MC1R, MC3R, MC4R, and MC5R, with preferential affinity for MC3R and MC4R subtypes. Structure-activity relationship studies compare the cyclic constraint and D-Phe substitution to linear α-MSH analogs, examining how conformational rigidity influences receptor subtype selectivity and signaling bias in cell-based reporter assays.

Hadley ME, Dorr RT. “Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization.” Peptides. 2006. PubMed

MC4R activation by melanocortin agonists modulates sympathetic and parasympathetic outflow through central autonomic circuits. Pharmacological studies characterize the relationship between MC4R engagement and cardiovascular parameters including blood pressure and heart rate in preclinical models. These effects are mediated through brainstem autonomic nuclei receiving melanocortinergic projections from the hypothalamus. Research compound — not for human use.

Greenfield JR et al. “Melanocortin signalling and the regulation of blood pressure in human obesity.” J Neuroendocrinol. 2009. PubMed