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 epilepsy.
Taken 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.