Anticonvulsants that don't fit the classic Na+ channel or GABA-A pattern. Gabapentin + pregabalin bind α2δ-1 auxiliary subunit of voltage-gated Ca²⁺ channels → reduce neurotransmitter release at presynaptic terminals (covered in calcium_channel_modulation as well). Topiramate has multiple actions: Na+ channel block + GABA-A enhancement + AMPA inhibition + carbonic anhydrase inhibition — partly explains its broad anticonvulsant + migraine + weight-loss profile. Zonisamide has a similar broad-target profile. Levetiracetam binds SV2A (synaptic vesicle glycoprotein 2A) → modulates presynaptic vesicle release; novel mechanism, clean DDI profile. Brivaracetam is a higher-affinity SV2A ligand. Ethosuximide blocks thalamic T-type Ca²⁺ — covered in calcium_channel_modulation; absence-seizure specific. Rufinamide for Lennox-Gastaut.
Organ Systems
nervous
Pathway Steps
presynaptic-vesicle-pool → neurotransmitter-release — via SV2A scaffolds vesicle release; levetiracetam family target. Gabapentin and pregabalin bind the α2δ auxiliary subunit of presynaptic voltage-gated calcium channels, reducing calcium-dependent release of excitatory neurotransmitters from hyperexcitable neurons. Despite their names they do not act on GABA receptors — this α2δ mechanism underlies their use in neuropathic pain and partial seizures.