Drugs acting at TRPM7 channels inhibit seizure-like activity

Epilepsia Open. 2023 Sep;8(3):1169-1174. doi: 10.1002/epi4.12773. Epub 2023 Jun 20.

Abstract

Transient receptor potential cation subfamily M7 (TRPM7) channels are ion channels permeable to divalent cations. They are abundantly expressed with particularly high expression in the brain. Previous studies have highlighted the importance of TRPM7 channels in brain diseases such as stroke and traumatic brain injury, yet evidence for a role in seizures and epilepsy is lacking. Here, we show that carvacrol, a food additive that inhibits TRPM7 channels, and waixenicin A, a novel selective and potent TRPM7 inhibitor, completely suppressed seizure-like activity in rodent hippocampal-entorhinal brain slices exposed to pentylenetetrazole or low magnesium. These findings support inhibition of TRPM7 channels as a novel target for antiseizure medications.

Keywords: TRPM7; carvacrol; epilepsy; seizure; waixenicin A.

MeSH terms

  • Acetates
  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use
  • Cymenes* / pharmacology
  • Cymenes* / therapeutic use
  • Disease Models, Animal
  • Diterpenes
  • Hippocampus / drug effects
  • Male
  • Mice
  • Pentylenetetrazole*
  • Rats
  • Seizures* / drug therapy
  • TRPM Cation Channels* / antagonists & inhibitors
  • TRPM Cation Channels* / drug effects

Substances

  • TRPM Cation Channels
  • Pentylenetetrazole
  • carvacrol
  • Cymenes
  • waixenicin A
  • Anticonvulsants
  • Trpm7 protein, mouse
  • Acetates
  • Diterpenes