Substance P

Summary

Substance P is an 11-amino acid neuropeptide (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2) first isolated in 1931. It is an endogenous neurotransmitter and neuromodulator involved in pain signaling, neurogenic inflammation, emesis, mood regulation, and immune modulation. It is not approved as a therapeutic agent but is widely used as a research tool. NK1 receptor antagonists (e.g., aprepitant) have been developed as indirect modulators of its pathway.

Mechanism of Action

Binds preferentially to the neurokinin 1 (NK1) receptor, a G-protein-coupled receptor, activating phospholipase C and increasing intracellular calcium. Mediates pain transmission, neurogenic inflammation, vasodilation, and smooth muscle contraction. Also activates NK2 and NK3 receptors at higher concentrations.

Routes of Administration

Goals & Uses

• Pain research / nociception modulationResearchHigh
• Depression / anxiety researchResearchModerate
• Wound healing (investigational)Investigational TherapeuticLow
• Emesis / nausea researchResearchHigh
• Neurogenic inflammation characterizationResearchHigh

Contraindications

• Chronic pain conditions requiring stable managementPainModerate
• Severe hypotension or cardiovascular instabilityCardiovascularHigh
• Hypersensitivity to Substance P or tachykininsAllergyHigh

Adverse Effects

• HypotensionCardiovascularCommonLow blood pressure
• Nausea/vomitingGastrointestinalUncommon
• FlushingVascularCommonWarmth and redness of the skin
• Increased vascular permeability / edemaInflammatoryCommon
• Pain or burning at injection siteLocalCommon
• BronchoconstrictionRespiratoryUncommon

Drug Interactions

• Aprepitant / FosaprepitantHigh
• ACE inhibitors (e.g., captopril, enalapril)Moderate
• Neutral endopeptidase inhibitors (neprilysin inhibitors)Moderate
• Opioids (e.g., morphine)Low

Population Constraints

• Asthma / reactive airway diseasePulmonaryRelative
• PregnancyReproductive SafetyRelative
• Pediatric populationsAgeRelative
• Patients with inflammatory bowel diseaseGastrointestinalRelative

Regulatory Status

• European UnionUnapprovedNot EMA-approved. Research use only.
• United StatesUnapprovedNot FDA-approved as a therapeutic. Used in research under IND or institutional protocols.
• United KingdomUnapprovedNot MHRA-approved. Available for laboratory and clinical research use only.

Not approved by FDA, EMA, or MHRA as a therapeutic drug. Used extensively in preclinical and clinical research. NK1 receptor antagonists targeting the Substance P pathway are approved for chemotherapy-induced nausea and vomiting.

Evidence & Sources

No sources recorded yet.