Background: Epilepsy is a neurological disorder manifested by recurrent episodes
of seizures, loss of consciousness, and sensory disturbances. Epileptic seizure is generated
due to functional disturbance within the population of neurons. The present study was conducted
to evaluate the effect of various classical neurotransmitter and neuropeptides in epilepsy
in humans as well as in rodents.
Objectives: The present study reviews the role of various brain neurotransmitters viz. GABA,
glutamate, biogenic amines, and neuropeptides in the prevention and regulation of epileptic
seizure in humans as well as in various animal models of epilepsy.
Discussion: We provide evidences, from various clinical and pre-clinical studies, regarding
role of individual brain neurotransmitters in the pathophysiology of Epilepsy. Gamma
Aminobutyric Acid (GABA) hypoactivity induces dopamine hyperactivity as dopaminergic
neurons are affected by the inhibitory influence of the GABAergic system through GABA
(A) receptors. Glutamate hyperactivity is exerted via presynaptic N-methyl-D-aspartate
(NMDA) receptors and postsynaptic ionotropic glutaminergic receptors that strongly inhibit
serotoninergic neurons and induce epileptic seizures, respectively. This study suggests that
there is an increase in the electrical activity of cortex on topical application of Ach following
the administration of pentylenetetrazole. However, the neuropeptides like substance increase
the glutamate-dependent excitotoxicity by acting on the NK1 receptors. The study also suggests
the involvement of nitric oxide mechanism in epilepsy by over-activation of NMDA receptors.
The endocannabinoids, such as Cannabinoids produce neuroprotective effects by antagonistic
action on NMDA receptors and inverse agonism on CB1 receptors. However, the
chronic overexpression of Adenosine Kinase (ADK) causes seizures in epilepsy. The anticonvulsant
actions of adenosine are mainly mediated via activation of A1 receptors.
Conclusion: Thus, the present review suggests a possible involvement of neurotransmitter
and neuropeptides in epilepsy in humans and rodents.