TRPV1 Channel: A Potential Drug Target for Treating Epilepsy

Abstract

Epilepsy has 2-3% incidence worldwide. However, present antiepileptic drugs provide only partial control of seizures. Calcium ion accumulation in hippocampal neurons has long been known as a major contributor to the etiology of epilepsy. TRPV1 is a calcium-permeable channel and mediator of epilepsy in the hippocampus. TRPV1 is expressed in epileptic brain areas such as CA1 area and dentate gyrus of the hippocampus. Here the author reviews the patent literature on novel molecules targeting TRPV1 that are currently being investigated in the laboratory and are candidates for future clinical evaluation in the management of epilepsy. A limited number of recent reports have implicated TRPV1 in the induction or treatment of epilepsy suggesting that this may be new area for potential drugs targeting this debilitating disease. Thus activation of TRPV1 by oxidative stress, resiniferatoxin, cannabinoid receptor (CB1) activators (i.e. anandamide) or capsaicin induced epileptic effects, and these effects could be reduced by appropriate inhibitors, including capsazepine (CPZ), 5'-iodoresiniferatoxin (IRTX), resolvins, and CB1 antagonists. It has been also reported that CPZ and IRTX reduced spontaneous excitatory synaptic transmission through modulation of glutaminergic systems and desensitization of TRPV1 channels in the hippocampus of rats. Immunocytochemical studies indicated that TRPV1 channel expression increased in the hippocampus of mice and patients with temporal lobe epilepsyTaken together, findings in the current literature support a role for calcium ion accumulation through TRPV1 channels in the etiology of epileptic seizures, indicating that inhibition of TRPV1 in the hippocampus may possibly be a novel target for prevention of epileptic seizures.

The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels

“…Accumulating evidences indicated that activations of TRPM2 and TRPV1 channels are increased in brain injury-induced mitochondrial activation and excessive Free oxygen radical production by the excessive mitochondrial Ca 2+ uptake6929. Furthermore, DEX induces antioxidant effects in the spinal cord (DRG) injuries and cerebral ischemia (hippocampus) of rats11819.…”

“…Transient receptor potential (TRP) family is containing 8 subfamily. Melastatin and vanilloid subfamilies include TRP melastatin 2 (TRPM2) and TRP vanilloid 1 (TRPV1) Ca 2+ permeable cation channels49. Capsaicin (CAP) is a pungent component of hot chili peppers, and TRPV1 is activated by different stimuli, including CAP 10 and oxidative stress11.…”

Antinociceptive effect of natural and synthetic alkamides involves TRPV1 receptors

“…Blockade of TRPV1 channels by capsazepine administration remarkably suppressed in vivo ongoing ictal activity . Recently, Nazıroğlu presents a revision that support a role for Ca 2+ accumulation through TRPV1 channels in the aetiology of epileptic seizures, indicating that inhibition of TRPV1 in the hippocampus may possibly be a novel target for prevention of epileptic seizures …”

Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists

“…A growing number of recent studies indicate the involvement of TRPV1 receptors in the etiopathogenesis of epilepsy . Very recently, functional TRPV1 channels have been found in the hippocampus, an epileptic area of the brain.…”