Somatostatin: an endogenous antiepileptic.

The neuropeptide somatostatin (SST) is highly expressed in brain regions associated with seizures. In hippocampus, SST expression and release is regulated by seizures, and SST-containing neurons within the hilus of the dentate gyrus are sensitive to seizure-induced death. In vivo and in vitro studies suggest that the loss of SST function in the dentate could contribute to epileptogenesis and seizure susceptibility. SST also has inhibitory actions in the CA1 and CA3 hippocampus indicating this peptide is an important homeostatic regulator throughout the hippocampus. In vivo studies show SST has robust antiepileptic properties with the major site of action being hippocampus. In rodents, somatostatin receptor subtype 2 (SST(2)) and SST(4) appear to mediate the majority of the antiepileptic actions of SST, with SST(2) predominate in rat and SST(4) in mouse. Thus SST receptors may be appropriate targets for new antiepileptic drugs (AEDs), although validation in human tissue is lacking.