Sigma-1 receptor antagonists: promising players in fighting neuropathic pain

Pharm Pat Anal. 2020 May;9(3):77-85. doi: 10.4155/ppa-2020-0007. Epub 2020 Jun 16.

Abstract

Sigma-1 receptors (S1Rs) are strongly correlated to neuropathic pain (NP), since their inactivation may decrease allodynia or dysesthesia, promoting analgesic effects. In the recent patent landscape, S1R antagonists endowed with nanomolar S1Rs affinity emerged as potent antinociceptive agents. So far, three patented compounds have been proposed for counteracting NP. Particularly PV-752 and AV1066, disclosed by the University of Pavia (Italy) and Anavex, respectively, showed good analgesic activity in preclinical studies. Moreover, E-52862 developed by Esteve (Spain) has been proved to be effective, both in preclinical and Phase II clinical trials, against several symptoms of NP. These patents ascertain S1R antagonists as potential drugs, alone or in combination with other analgesic drugs, for managing NP in humans.

Keywords: E-52862; MR309; PV-752; chemotherapy-induced peripheral neuropathy; neuropathic pain; postherpetic neuralgia; sigma-1 receptor antagonist.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / chemistry
  • Analgesics, Opioid / pharmacology
  • Analgesics, Opioid / therapeutic use
  • Animals
  • Humans
  • Methadone / chemistry
  • Methadone / pharmacology
  • Methadone / therapeutic use
  • Narcotic Antagonists / chemistry
  • Narcotic Antagonists / pharmacology
  • Narcotic Antagonists / therapeutic use*
  • Neuralgia / drug therapy*
  • Neuralgia / metabolism
  • Nortriptyline / chemistry
  • Nortriptyline / pharmacology
  • Nortriptyline / therapeutic use
  • Patents as Topic* / legislation & jurisprudence
  • Receptors, sigma / antagonists & inhibitors*
  • Receptors, sigma / metabolism
  • Sigma-1 Receptor
  • Tramadol / chemistry
  • Tramadol / pharmacology
  • Tramadol / therapeutic use

Substances

  • Analgesics, Opioid
  • Narcotic Antagonists
  • Receptors, sigma
  • Tramadol
  • Nortriptyline
  • Methadone