Description
PT-141 (Bremelanotide) – Advanced Biochemical Mechanism Profile
(Melanocortin receptor agonist; synthetic α-MSH analogue)
PT-141 is a cyclic heptapeptide that primarily activates melanocortin receptors MC3R and MC4R, which are G-protein–coupled receptors (GPCRs) expressed in central nervous system pathways associated with autonomic and neuroendocrine signaling. Unlike melanotan II, PT-141 does not require peripheral nitric oxide pathways and acts directly at central melanocortin receptors in research models.
✅ 1. Primary Molecular Targets
Melanocortin Receptors
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MC4R (Melanocortin-4 receptor) – main target
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MC3R – secondary affinity
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GPCR family, coupled predominantly to Gs proteins
Ligand binding induces:
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MC4R activation
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Gsα stimulation
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Adenylyl cyclase activation
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↑ cAMP
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PKA activation
✅ 2. Intracellular Signaling Pathways
A. cAMP / Protein Kinase A (PKA)
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cAMP accumulation triggers PKA phosphorylation of:
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Voltage-gated ion channels
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Synaptic signaling proteins
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Transcription factors (CREB)
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cAMP-responsive genes commonly monitored:
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CREB-regulated genes
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BDNF
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c-Fos
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EGR1
B. MAPK / ERK Pathway
Some neuronal model studies show:
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MC4R → Ras → Raf → MEK → ERK1/2
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ERK1/2 nuclear translocation → immediate early gene transcription
ERK-responsive genes:
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FOS, JUN, ARC, EGR1
C. PLC / IP3 / DAG (Less dominant)
In certain MC4R-expressing cell lines:
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Gq coupling may occur
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Activation of PLCβ
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IP₃ → Ca²⁺ release
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DAG → PKC signaling
This pathway generally complements, rather than replaces, cAMP signaling.
✅ 3. Neurotransmitter Modulation in Research Models
MC3R/MC4R activation can influence:
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Hypothalamic neuronal firing
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Autonomic output pathways
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Dopaminergic circuits
Measured biochemical markers include:
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c-Fos induction in hypothalamic neurons
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Modulation of dopamine turnover genes (TH, DAT, DRD1) in select models
(No claims of clinical effect—only documented in vitro/in situ experimental systems.)
✅ 4. Second Messengers & Downstream Enzymes
| Component | Mechanistic Effect |
|---|---|
| cAMP ↑ | Primary signaling mediator |
| PKA | Phosphorylation of CREB & membrane proteins |
| CREB | Transcription of immediate early genes |
| ERK1/2 | Gene expression & synaptic plasticity pathways |
| Ca²⁺ flux | In some Gq-linked MC4R systems |
✅ 5. Representative Gene Targets
Researchers frequently monitor expression of:
| Category | Genes Commonly Assayed |
|---|---|
| Immediate-early genes | FOS, JUN, EGR1, ARC |
| CREB-responsive genes | BDNF, NR4A1, c-Fos |
| Neurotransmission | TH (tyrosine hydroxylase), DRD1, DRD2, DAT |
| Synaptic plasticity | CAMKII, SYN1 |
✅ Mechanistic Summary
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Synthetic α-MSH analogue
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MC4R/MC3R GPCR agonist
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Activates Gs → adenylyl cyclase → cAMP → PKA → CREB
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Can involve ERK/MAPK and occasional PLC/IP₃/PKC signaling
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Drives transcription of cAMP/CREB-responsive genes in neuronal models
Research-Only Classification
PT-141 is provided solely for in-vitro laboratory research.
Not for human or animal administration, therapeutic use, or biological application outside controlled research settings.