Product Research Profile: PT-141 & PL-6983 in Ischemia Reperfusion Models

I. Introduction

This document provides a technical profile for the research agent PT-141 (Bremelanotide) and its variant, PL-6983, for use in controlled laboratory settings focused on critical care and tissue perfusion models, specifically Ischemia Reperfusion (I/R) injury. The data summarized herein supports the application of these agents as specialized tools for investigating sympathetic nervous system modulation in acute physiological stress.

II. Product Details and Restrictions

Compound

Alternative Name

CAS Number

Formulation

PT-141

Bremelanotide

189691-06-3

Lyophilized powder

PL-6983

[Placeholder]

[Placeholder]

Lyophilized powder

Restriction: This product is strictly for laboratory experimentation and research purposes only. It is not for human or veterinary use. All handling and disposal must comply with institutional biosafety and chemical hygiene protocols.

III. Research Context: Emerging Applications in Critical Care Models

Emerging preclinical research highlights the potential role of melanocortin receptor agonists, specifically PT-141 and PL-6983, in modulating acute physiological responses characteristic of severe trauma and shock. The primary focus of current research involves their influence on tissue oxygenation and damage mitigation during periods of reduced blood flow and subsequent reperfusion.

A. Hypovolemia and Hemorrhagic Shock

Studies in various animal models, predominantly rat models of controlled hemorrhagic shock, demonstrate that PT-141 administration can confer protective effects against the consequences of severe blood loss.

• Ischemia Reduction: The agent appears to reduce the degree of tissue ischemia and subsequent cellular damage typically observed during severe hypovolemia. This protective effect suggests a mechanism that stabilizes critical tissue function despite circulatory compromise.
• Tissue Damage Mitigation: Histological and biochemical analyses post-shock often show reduced markers of cellular necrosis and inflammation in PT-141 treated groups compared to controls.

B. Resuscitation and Tissue Perfusion

A critical area of investigation involves the agent's ability to maintain or restore tissue perfusion and oxygen balance, potentially independent of standard fluid resuscitation volumes.

Key Research Observation

Implication

Required Research Assay

Reduced Oxygen Debt

Suggests improved efficiency of oxygen delivery or utilization at the cellular level.

Measuring Arterial-Venous O₂ difference

Maintained Perfusion

Indicates a sympathetically-mediated shift in microvascular blood flow regulation.

Laser Doppler flowmetry in target organs

Reduced I/R Injury

Central to application in surgical, trauma, and transplant models.

Infarct size determination (e.g., TTC staining)

IV. Mechanism of Action

Both PT-141 and PL-6983 are potent agonists of the Melanocortin Receptor system. Their mechanism in I/R injury is primarily attributed to activity at the Melanocortin 4 Receptor (MC4R).

1. MC4R Binding: The agent binds selectively to the MC4R, which is expressed in various tissues, notably the Central Nervous System (CNS) and peripheral neural pathways.
2. Sympathetic Modulation: Activation of MC4R leads to the modulation of the Sympathetic Nervous System (SNS) activity. This modulation is hypothesized to result in a protective shift in cardiovascular and microvascular tone, preventing the excessive vasoconstriction and tissue shutdown often seen in severe shock states.

V. Recommended Laboratory Applications

A. Hemorrhage and Shock Models

These compounds are essential tools for laboratories investigating novel resuscitation strategies.

• Model Type: Controlled hemorrhagic shock (e.g., Wigger's model).
• Endpoints: Mean Arterial Pressure (MAP) stabilization, survival rates, tissue lactate levels, and base deficit.
• Dose Response: Future studies should focus on establishing optimal timing and dosing protocols for PT-141 administration relative to the onset of shock.

B. Ischemia-Reperfusion Injury Assays

I/R injury is a fundamental challenge in trauma, transplant surgery, and myocardial infarction research.

• Target Organs: Suitable for use in models involving cerebral ischemia (stroke), myocardial ischemia, renal ischemia, and intestinal ischemia-reperfusion models.
• Assays: Assessment typically involves measuring infarct size, evaluating organ function biomarkers (e.g., creatinine, troponin), and measuring pro-inflammatory cytokine profiles (IL-6, TNF-α).

C. Future Research Directions

A primary goal for current research is the comparative study between PT-141 and PL-6983 to delineate potential differences in pharmacokinetics, receptor selectivity, and downstream signaling effects, particularly concerning their impact on tissue viability.

A link to the safety and material data sheet for the compound can be found here: File.

VI. Research Protocol Planning Checklist

Investigators planning studies utilizing PT-141 or PL-6983 should ensure the following steps are completed prior to the study start date of Date:

1. Institutional Review Board (IRB) Approval: Confirmation of ethical clearance for animal use (File).
2. Inventory Check: Verify sufficient stock of the research agent.
3. Experimental Setup: Confirm the availability of necessary monitoring equipment (e.g., blood pressure monitors, blood gas analyzers).
4. Team Training: Ensure all research personnel, including Person, are trained in the specific I/R model being used. The next training session is scheduled for Calendar event at Place.

Task

Status

Completion Date

Develop Standard Operating Procedure (SOP)

In Progress

Date

Secure Animal Housing

Complete

Date

Calibrate Monitoring Equipment

Pending

Date

Final Protocol Review with PI

Scheduled

Date

VII. Conclusion

PT-141 and PL-6983 represent valuable agents for advancing research into the physiological response to shock and ischemia-reperfusion injury. Their unique mechanism of action via MC4R modulation offers a non-traditional pathway for mitigating tissue damage in acute, life-threatening conditions. Rigorous, controlled laboratory experimentation is essential to fully characterize their therapeutic potential and translate these findings into clinical understanding.