Spantide I TFA

Names

[ Name ]:
Spantide I TFA

[Synonym ]:
M.W. 1497.80 C75H108N20O13
SPANTIDE
1-Arg-7,9-Trp-11-Leu-substance p
SPANTIDE HYDROCHLORIDE
Spantide I
Substance P-[D-Arg1,D-Trp7,9,Leu11]

Biological Activity

[Description]:

Spantide I, a substance P analog, is a selective NK1 receptor antagonist, with Ki values of 230 nM and 8150 nM for NK1 and NK2 receptor, respectively. Spantide I provides an approach to reduce type 1 and enhance the type 2 cytokine IL-10 in the infected cornea, leading to a significant reduction in corneal perforation[1][2][3].

[Related Catalog]:

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Neuronal Signaling >> Neurokinin Receptor

Signaling Pathways >> GPCR/G Protein >> Neurokinin Receptor

[Target]

NK1:230 nM (Ki)

NK2:8150 nM (Ki)

[In Vivo]

Spantide I (50 and 100 nM perfused through the cerebral ventricles) causes a complete respiratory arrest in all of the examined animals[2]. Spantide I (36 μg/mouse, ip daily) significantly decreases the number of perforated corneas, bacterial counts, and PMNs. Spantide I also downregulates the mRNA levels for type I cytokines (e.g., IFN-γ) as well as MIP-2, IL-6, TNF-α, and IL-1β[3]. Animal Model: Female, 8-week-old C57BL/6 (B6) and BALB/c mice[3]. Dosage: 36 μg/mouse. Administration: IP on days -1 and 0 (day of infection) and daily through 5 days pi (post infection). Result: At 3 and 5 days pi, compound-treated mice had significantly less severe ocular disease than did the PBS-treated mice. Contained significantly fewer PMNs than the corneas of PBS-treated mice at 3 and 5 days pi. Significantly reduced levels of corneal TNF-α mRNA at 3 and 5 days pi. Significantly reduced the level of IL-18 mRNA at 1 day pi.

[References]

[1]. J C Beaujouan, et al. Higher potency of RP 67580, in the mouse and the rat compared with other nonpeptide and peptide tachykinin NK1 antagonists. Br J Pharmacol. 1993 Mar;108(3):793-800.

[2]. M Zubrzycka, et al. Comparison of antagonistic properties of substance P analogs, spantide I, II and III, on evoked tongue jerks in rats. Endocr Regul. 2000 Mar;34(1):13-8.

[3]. Linda D Hazlett, et al. Spantide I decreases type I cytokines, enhances IL-10, and reduces corneal perforation in susceptible mice after Pseudomonas aeruginosa infection. Invest Ophthalmol Vis Sci. 2007 Feb;48(2):797-807.

Chemical & Physical Properties

[ Molecular Formula ]:
C₇₅H₁₀₈N₂₀O₁₃

[ Molecular Weight ]:
1497.79000

[ Exact Mass ]:
1496.84000

[ PSA ]:
548.21000

[ LogP ]:
7.06100

[ Storage condition ]:
-20°C

Safety Information

Articles

Involvement of midbrain tectum neurokinin-mediated mechanisms in fear and anxiety.

Braz. J. Med. Biol. Res. 45(4) , 349-56, (2012)

Electrical stimulation of midbrain tectum structures, particularly the dorsal periaqueductal gray (dPAG) and inferior colliculus (IC), produces defensive responses, such as freezing and escape behavio...

Solution conformation of Substance P antagonists-[D-Arg1, D-Trp7,9, Leu11]-SP, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP and [D-Pro2, D-Trp7,9]-SP by CD, NMR and MD simulations.

Peptides 26 , 875-885, (2005)

Substance P (SP) is an important neuropeptide involved in pain transmission and induction of inflammation. Its antagonists are being extensively investigated for their non-narcotic analgesic and anti-...

Substance P stimulates late-stage rat osteoblastic bone formation through neurokinin-1 receptors.

Neuropeptides 41(1) , 25-31, (2007)

Substance P (SP) is a widely distributed neuropeptide that works as a neurotransmitter and neuromodulator. Recently, SP receptors, particularly neurokinin-1 receptors (NK(1)-Rs) that have a high affin...