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Record Information
StatusDetected and Quantified
Creation Date2006-03-08 15:00:54 UTC
Update Date2019-01-11 19:16:20 UTC
Secondary Accession Numbers
  • HMDB01897
Metabolite Identification
Common NameSubstance P
DescriptionSubstance P (SP), is an 11-amino acid neuropeptide. SP is a member of the tachykinin family of peptides because it induces rapid smooth muscle contraction in guinea pig ileum and rat duodenum. Other members of the tachykinin family, sharing common carboxyl terminal Phe-X-Gly-Leu-met-NH2 sequences in mammals, include neurokinin A and neurokinin B. In mammals, tachykinins are produced by two genes, preprotachykinin-A (PPT-A) and preprotachykinin-B (PPT-B), and SP is a product of the PPT-A gene. SP is localized in the central nervous system as well as in several peripheral tissues, including the entire length of the gastrointestinal tract as well as the colon. The main sources of SP in the gut include the myenteric and submucosal plexus, intrinsic sensory neurons, as well as sensory neurons originating from the dorsal root ganglia. A newly identified gene, preprotachykinin C gene, encodes for the sequence of a new preprotachykinin protein designated hemokinin (HK) and produced primarily by hematopoietic cells. HK binds with high selectivity to NK-1R and has similar in vivo potency to SP. Like SP, HK is an 11-amino acid peptide having ~55% amino acid similarity to SP. The effects of SP are mediated by three different G-protein-coupled receptors (GPCRs), namely neurokinin (NK)-1, 2, and 3. SP binds with high affinity to NK-1 receptor (NK-1R), and with low affinity to NK-2 and 3 receptors. NK-1 receptors are present in both small intestine and colon of animals and humans and are localized in a variety of cells, including nerves, smooth muscle, immune cells, glands, endothelial cells, as well as epithelial cells. Although NK-1 receptors have been associated with several intestinal pathophysiologic conditions (see below), NK-2 receptors have been linked mostly with circular muscle contraction, and are localized in circular muscle and muscularis mucosae. Although NK-2 receptors are present predominantly on smooth muscle and, like NK-1, can affect gut motility, NK-3 receptors are expressed predominantly in neurons and can stimulate or diminish muscle contraction indirectly following SP binding to neuronal cells in the submucosal and myenteric nerve plexuses of the gastrointestinal tract. NK-3 receptors also provide slow excitatory synaptic input to neurons in ganglia of the sphincter of Oddi. Thus, both NK-2 and NK-3 receptors affect motility responses in the GI, but there is very little evidence that they are involved in neuroimmune interactions. (PMID: 17192554 ).
(2S)-2-{[(2R)-2-({[(2S)-1-[(2S)-6-amino-2-({[(2R)-1-[(2S)-2-amino-5-carbamimidamidopentanoyl]pyrrolidin-2-yl](hydroxy)methylidene}amino)hexanoyl]pyrrolidin-2-yl](hydroxy)methylidene}amino)-1-hydroxy-4-(C-hydroxycarbonimidoyl)butylidene]amino}-N-[(1R)-1-{[(1R)-1-[({[(1R)-1-{[(1S)-1-(C-hydroxycarbonimidoyl)-3-(methylsulphanyl)propyl]-C-hydroxycarbonimidoyl}-3-methylbutyl]-C-hydroxycarbonimidoyl}methyl)-C-hydroxycarbonimidoyl]-2-phenylethyl]-C-hydroxycarbonimidoyl}-2-phenylethyl]pentanediimidic acidGenerator
Chemical FormulaC63H98N18O13S
Average Molecular Weight1347.63
Monoisotopic Molecular Weight1346.728146002
IUPAC Name(2S)-2-[(2R)-2-{[(2S)-1-[(2S)-6-amino-2-{[(2R)-1-[(2S)-2-amino-5-carbamimidamidopentanoyl]pyrrolidin-2-yl]formamido}hexanoyl]pyrrolidin-2-yl]formamido}-4-carbamoylbutanamido]-N-[(1R)-1-{[(1R)-1-[({[(1R)-1-{[(1S)-1-carbamoyl-3-(methylsulfanyl)propyl]carbamoyl}-3-methylbutyl]carbamoyl}methyl)carbamoyl]-2-phenylethyl]carbamoyl}-2-phenylethyl]pentanediamide
Traditional Name(2S)-2-[(2R)-2-{[(2S)-1-[(2S)-6-amino-2-{[(2R)-1-[(2S)-2-amino-5-carbamimidamidopentanoyl]pyrrolidin-2-yl]formamido}hexanoyl]pyrrolidin-2-yl]formamido}-4-carbamoylbutanamido]-N-[(1R)-1-{[(1R)-1-[({[(1R)-1-{[(1S)-1-carbamoyl-3-(methylsulfanyl)propyl]carbamoyl}-3-methylbutyl]carbamoyl}methyl)carbamoyl]-2-phenylethyl]carbamoyl}-2-phenylethyl]pentanediamide
CAS Registry Number33507-63-0
InChI Identifier
Chemical Taxonomy
Description belongs to the class of organic compounds known as medium-chain fatty acids. These are fatty acids with an aliphatic tail that contains between 4 and 12 carbon atoms.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentMedium-chain fatty acids
Alternative Parents
  • Medium-chain fatty acid
  • Amino fatty acid
  • Straight chain fatty acid
  • Amino acid or derivatives
  • Amino acid
  • Carboxylic acid derivative
  • Carboxylic acid
  • Monocarboxylic acid or derivatives
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Primary aliphatic amine
  • Amine
  • Carbonyl group
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Physiological effect

Health effect:


Route of exposure:

Biological location:


Physical Properties
Experimental Properties
Melting Point148 °CNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
Water Solubility0.023 g/LALOGPS
pKa (Strongest Acidic)11.49ChemAxon
pKa (Strongest Basic)11.9ChemAxon
Physiological Charge3ChemAxon
Hydrogen Acceptor Count18ChemAxon
Hydrogen Donor Count16ChemAxon
Polar Surface Area516.63 ŲChemAxon
Rotatable Bond Count42ChemAxon
Refractivity362.14 m³·mol⁻¹ChemAxon
Polarizability141.28 ųChemAxon
Number of Rings4ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-02wa-1319101010-209f8038eedc515a4d6fJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-02ta-2729101110-7d4d3932d047407e1218JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-02mj-9835202000-3628a96e37d0d507d9c7JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0f92-6079000000-c6a896a4135dad2d4620JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-9133000000-514803d766a008324128JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0002-9101000000-1af52acc0df0cbc52a65JSpectraViewer | MoNA
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Urine
Tissue LocationsNot Available
Normal Concentrations
BloodDetected and Quantified0.0000036 +/- 0.0000018 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.323-1.07 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000007 +/- 0.0000006 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000141 +/- 0.0000142 uMNewborn (0-30 days old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.022673 +/- 0.00834 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0227 +/- 0.0083 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00005 +/- 0.0000023 uMChildren (1-13 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000095 +/- 0.0000015 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000196 +/- 0.0000032 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000144 +/- 0.0000042 uMNot SpecifiedNot SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000007425 +/- 0.00000007425 uMNot SpecifiedNot Specified
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000008910 +/- 0.0000005940 uMNot SpecifiedNot Specified
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000123 +/- 0.0000028 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00002339 +/- 0.000001188 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00002354 +/- 0.000001559 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00002309 +/- 0.000001782 uMAdult (>18 years old)Not SpecifiedNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000439 +/- 0.0000099 uMAdult (>18 years old)Not SpecifiedNormal details
Abnormal Concentrations
BloodDetected and Quantified0.0000049 +/- 0.0000027 uMAdult (>18 years old)Both
Cerebrospinal Fluid (CSF)Detected and Quantified1.37-16.3 uMNot SpecifiedNot SpecifiedCobalamin deficiency details
Cerebrospinal Fluid (CSF)Detected and Quantified0.000864 +/- 0.0003576 uMNewborn (0-30 days old)Not SpecifiedSpina Bifida details
Cerebrospinal Fluid (CSF)Detected and Quantified0.15 uMNot SpecifiedNot SpecifiedSpina Bifida details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00025 +/- 0.0000282 uMNewborn (0-30 days old)Not SpecifiedPremature details
Cerebrospinal Fluid (CSF)Detected and Quantified1.41e-4 +/- 1.42e-05 uMNewborn (0-30 days old)Not SpecifiedFull term newborn details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000361 +/- 0.0000027 uMNot SpecifiedNot SpecifiedFibromyalgia details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000401 +/- 0.0000027 uMAdult (>18 years old)Not SpecifiedFibromyalgia details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000292 +/- 0.000005 uMNot SpecifiedNot SpecifiedFibromyalgia details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000351 +/- 0.0000032 uMNot SpecifiedNot SpecifiedFibromyalgia details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000192 +/- 0.0000067 uMNot SpecifiedNot SpecifiedSleep Apnea Syndrome details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000009653 +/- 0.0000008910 uMNot SpecifiedNot Specified
Chronic headache
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000005198 +/- 0.0000003713 uMNot SpecifiedNot Specified
Chronic headache
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000199 +/- 0.0000039 uMAdult (>18 years old)Not SpecifiedTerm Pregnancy details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00002176 +/- 0.000001188 uMAdult (>18 years old)Not SpecifiedAlzheimer's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00003111 +/- 0.000002822 uMAdult (>18 years old)Not SpecifiedAlzheimer's disease details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00002658 +/- 0.000002153 uMAdult (>18 years old)Not SpecifiedNon-Alzheimer dementias details
Cerebrospinal Fluid (CSF)Detected and Quantified0.00002562 +/- 0.0000009653 uMAdult (>18 years old)Not Specified
Neurological disorders without cognitive impairment
Cerebrospinal Fluid (CSF)Detected and Quantified0.00002770 +/- 0.0000020000 uMAdult (>18 years old)Not SpecifiedAlzheimer's Disease details
Cerebrospinal Fluid (CSF)Detected and Quantified0.0000303 +/- 0.0000078 uMAdult (>18 years old)Not SpecifiedNarcolepsy details
UrineDetected and Quantified0.0000098 +/- 0.0000036 umol/mmol creatinineAdult (>18 years old)FemaleMalignant solid neoplasm details
UrineDetected and Quantified0.000011 (0.0000005-0.000036) umol/mmol creatinineAdult (>18 years old)BothCisplatin containing chemotherapy details
Associated Disorders and Diseases
Disease References
  1. Fusayasu E, Kowa H, Takeshima T, Nakaso K, Nakashima K: Increased plasma substance P and CGRP levels, and high ACE activity in migraineurs during headache-free periods. Pain. 2007 Apr;128(3):209-14. Epub 2006 Nov 22. [PubMed:17123735 ]
Vitamin B12 deficiency
  1. Allen RH, Stabler SP, Savage DG, Lindenbaum J: Elevation of 2-methylcitric acid I and II levels in serum, urine, and cerebrospinal fluid of patients with cobalamin deficiency. Metabolism. 1993 Aug;42(8):978-88. [PubMed:8345822 ]
Spina Bifida
  1. Tam PK, Lister J: Elevation of cerebrospinal fluid substance P concentrations in spina bifida. Z Kinderchir. 1984 Dec;39 Suppl 2:89-90. [PubMed:6084371 ]
  1. Vaeroy H, Helle R, Forre O, Kass E, Terenius L: Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: new features for diagnosis. Pain. 1988 Jan;32(1):21-6. [PubMed:2448729 ]
  2. Vaeroy H, Sakurada T, Forre O, Kass E, Terenius L: Modulation of pain in fibromyalgia (fibrositis syndrome): cerebrospinal fluid (CSF) investigation of pain related neuropeptides with special reference to calcitonin gene related peptide (CGRP). J Rheumatol Suppl. 1989 Nov;19:94-7. [PubMed:2481742 ]
Sleep apnea
  1. Gislason T, Hedner J, Terenius L, Bisette G, Nemeroff CB: Substance P, thyrotropin-releasing hormone, and monoamine metabolites in cerebrospinal fluid in sleep apnea patients. Am Rev Respir Dis. 1992 Sep;146(3):784-6. [PubMed:1381567 ]
Alzheimer's disease
  1. Rosler N, Wichart I, Jellinger KA: Clinical significance of neurobiochemical profiles in the lumbar cerebrospinal fluid of Alzheimer's disease patients. J Neural Transm (Vienna). 2001;108(2):231-46. [PubMed:11314776 ]
  1. Strittmatter M, Isenberg E, Grauer MT, Hamann G, Schimrigk K: CSF substance P somatostatin and monoaminergic transmitter metabolites in patients with narcolepsy. Neurosci Lett. 1996 Nov 1;218(2):99-102. [PubMed:8945737 ]
Associated OMIM IDs
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDFDB002259
KNApSAcK IDNot Available
Chemspider ID23215821
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkSubstance P
METLIN IDNot Available
PubChem Compound44359816
PDB IDNot Available
ChEBI ID332416
Synthesis ReferenceEgorova, S. V.; Akhrem, A. A. Synthesis of substance P. Vestsi Akademii Navuk BSSR, Seryya Khimichnykh Navuk (1989), (1), 46-51.
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Koon HW, Pothoulakis C: Immunomodulatory properties of substance P: the gastrointestinal system as a model. Ann N Y Acad Sci. 2006 Nov;1088:23-40. [PubMed:17192554 ]
  2. Rothstein RD, Johnson E, Ouyang A: Substance P: mechanism of action and receptor distribution at the feline ileocecal sphincter region. Am J Physiol. 1989 Sep;257(3 Pt 1):G447-53. [PubMed:2476938 ]
  3. Grimsholm O, Rantapaa-Dahlqvist S, Dalen T, Forsgren S: Observations favouring the occurrence of local production and marked effects of bombesin/gastrin-releasing peptide in the synovial tissue of the human knee joint--comparisons with substance P and the NK-1 receptor. Neuropeptides. 2008 Apr;42(2):133-45. doi: 10.1016/j.npep.2007.12.008. [PubMed:18289674 ]
  4. Sequence Information [Link]


General function:
Involved in carboxylesterase activity
Specific function:
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name:
Uniprot ID:
Molecular weight:
  1. Lockridge O: Substance P hydrolysis by human serum cholinesterase. J Neurochem. 1982 Jul;39(1):106-10. [PubMed:6177830 ]
General function:
Involved in peroxidase activity
Specific function:
Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.
Gene Name:
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  1. Koon HW, Zhao D, Zhan Y, Rhee SH, Moyer MP, Pothoulakis C: Substance P stimulates cyclooxygenase-2 and prostaglandin E2 expression through JAK-STAT activation in human colonic epithelial cells. J Immunol. 2006 Apr 15;176(8):5050-9. [PubMed:16585602 ]
  2. Sio SW, Ang SF, Lu J, Moochhala S, Bhatia M: Substance P upregulates cyclooxygenase-2 and prostaglandin E metabolite by activating ERK1/2 and NF-kappaB in a mouse model of burn-induced remote acute lung injury. J Immunol. 2010 Nov 15;185(10):6265-76. doi: 10.4049/jimmunol.1001739. Epub 2010 Oct 6. [PubMed:20926798 ]
  3. Gallicchio M, Rosa AC, Benetti E, Collino M, Dianzani C, Fantozzi R: Substance P-induced cyclooxygenase-2 expression in human umbilical vein endothelial cells. Br J Pharmacol. 2006 Mar;147(6):681-9. [PubMed:16432508 ]
General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
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  1. Gobbetti A, Zerani M, Di Fiore MM, Botte V: Relationships among GnRH, substance P, prostaglandins, sex steroids and aromatase activity in the brain of the male lizard Podarcis sicula sicula during reproduction. J Reprod Fertil. 1994 Aug;101(3):523-9. [PubMed:7525952 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is:substance P > substance K > neuromedin-K
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