An update of 4‑aminopyride as a useful model of generalized seizures for testing antiseizure drugs: in vitro and in vivo studies

Abstract

Aminopyridines constitute a drug family with the ability to enhance synaptic transmission. In particular, 4‑aminopyridine (4‑AP) has been used as a model of generalized seizures. 4‑AP is a K+ channel blocker, but its mechanism of action has not yet been fully described; some evidence has shown that it acts on the K+ channel types Kv1.1, Kv1.2, Kv1.4 and Kv4, which are localized in the axonic terminals of pyramidal neurons and interneurons. When 4‑AP blocks the K+ channels it triggers depolarization and prolongs the action potential in the neuron, which causes nonspecific neurotransmitter release. Among these neurotransmitters, glutamate is the principal excitatory neurotransmitter released in the hippocampus. Once glutamate is released, it reaches its ionotropic and metabotropic receptors continuing the neuronal depolarization chain and propagation of hyperexcitability. This brief review is focused on the use of 4‑AP as an effective seizure model for testing antiseizure drugs in relevant in vitro and in vivo studies.