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An imidazole based H-Phe-Phe-NH 2 peptidomimetic with anti-allodynic effect in spared nerve injury mice
- Source :
- Bioorganic & Medicinal Chemistry Letters. 28:2446-2450
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- The dipeptide amide H-Phe-Phe-NH2 (1) that previously was identified as a ligand for the substance P 1-7 (SP1-7) binding site exerts intriguing results in animal models of neuropathic pain after central but not after peripheral administration. The dipeptide 1 is derived from stepwise modifications of the anti-nociceptive heptapeptide SP1-7 and the tetrapeptide endomorphin-2 that is also binding to the SP1-7 site. We herein report a strong anti-allodynic effect of a new H-Phe-Phe-NH2 peptidomimetic (4) comprising an imidazole ring as a bioisosteric element, in the spare nerve injury (SNI) mice model after peripheral administration. Peptidomimetic 4 was stable in plasma, displayed a fair membrane permeability and a favorable neurotoxic profile. Moreover, the effective dose (ED50) of 4 was superior as compared to gabapentin and morphine that are used in clinic.
- Subjects :
- 0301 basic medicine
Dipeptide
Membrane permeability
Tetrapeptide
Peptidomimetic
Organic Chemistry
Clinical Biochemistry
Pharmaceutical Science
Substance P
Nerve injury
Pharmacology
Ligand (biochemistry)
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
0302 clinical medicine
chemistry
Drug Discovery
Hyperalgesia
medicine
Molecular Medicine
medicine.symptom
Molecular Biology
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 0960894X
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Accession number :
- edsair.doi...........e57573a66b880d2115222e0c9b63598f