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Curr Med Chem. 2019 May 30. doi: 10.2174/0929867326666190530121133. [Epub ahead of print]

Targeting Neuropathic Pain: Pathobiology, Current Treatment and Peptidomimetics as a New Therapeutic Opportunity.

Author information

1
Department of Pharmacy and Health and Nutrition Sciences, University of Calabria, Edificio Polifunzionale, 87026 Rende (CS). Italy.
2
Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Polo Scientifico San Miniato, Via A. Moro 2, 53100 Siena. Italy.
3
Drug Discovery Unit, Ri.MED Foundation, Palermo, Italy
4
Department of Chemistry and Center of Advanced Studies in Chemistry, Panjab University, Chandigarh - 160014. India.
5
Department of Health Science, School of Medicine, University "Magna Grecia" of Catanzaro, Viale Europa, 88100 Catanzaro. Italy.

Abstract

There is a huge need for pharmaceutical agents for the treatment of chronic neuropathic pain (NP), a complex condition where patients can suffer from either hyperalgesia or allodynia originating from central or peripheral nerve injuries. To date, the therapeutic guidelines include the use of tricyclic antidepressant, serotonin noradrenaline reuptake inhibitors and anticonvulsants, beside the use of natural compounds and non-pharmacological options. Unfortunately, these drugs suffer from limited efficacy and serious dose-dependent adverse effects. In the last decades, the heptapeptide SP1-7, the major bioactive metabolite produced by substance P (SP) cleavage, has been largely investigated as a potential target for the development of novel peptidomimetic molecules to treat NP. Although the physiological effects of this SP fragment have been studied in detail, the mechanism behind its action is not fully clarified and the target for SP1-7 has not been identified yet. Nevertheless, specific binding sites for the heptapeptide have been found in brain and spinal cord of both mouse and rats. Several structure-affinity relationship (SAR) studies of SP1-7 and of some of its synthetic analogues have been carried out aiming to developing more metabolically stable and effective small molecule SP1-7 amide analogues that could be used as research tools for a better understanding of the SP1-7 system and, in a longer perspective, as potential therapeutic agents for future treatment of NP.

KEYWORDS:

Neuropathic; Substance P (SP) ; anticonvulsant; antidepressant; cannabinoids; erythromelalgia; inflammation; opioids

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