Neuropeptides are signaling molecules participating in the modulation of synaptic transmission. Neuropeptides
are stored in dense core synaptic vesicles, the release of which requires profound excitation. Only in the extracellular
space, neuropeptides act on G-protein coupled receptors to exert a relatively slow action both pre- and postsynaptically.
Consequently, neuropeptide modulators are ideal candidates to influence epileptic tissue overexcited during seizures. Indeed,
a number of neuropeptides have receptors implicated in epilepsy and many of them are considered to participate in
endogenous neuroprotective actions. Neuropeptide receptors, present in the hippocampus, the most frequent focus of seizures
in temporal lobe epilepsy, received the largest attention as potential anti-epileptic targets. Receptors of hippocampal
neuropeptides, somatostatin, neuropeptide Y, galanin, dynorphin, enkephalin, substance P, cholecystokinin, vasoactive intestinal
polypeptide, and receptors of some neuropeptides, which are also hormones such as ghrelin, angiotensins, corticotropin-
releasing hormone, adrenocorticotropin, thyrotropin-releasing hormone, oxytocin and vasopressin involved in epilepsy
are discussed in the review article. Activation and inhibition of receptors by oral application of peptides as drugs is
typically not efficient because of low bioavailability: rapid degradation and insufficient penetration of peptides through
the blood-brain barrier. Recent progress in the development of non-peptide agonists and antagonists of neuropeptide receptors
as well as gene therapeutic approaches leading to the local production of agonists and antagonists within the central
nervous system will also be discussed.