Why are benzodiazepines the first treatment for status epilepticus, and why do they work less the later they are given? · Grey Matter

Benzodiazepines act within minutes by making GABA-A receptors open more often, strengthening the inhibition that a seizure has overwhelmed, which is why guidelines put them first.

Why are benzodiazepines the first treatment for status epilepticus, and why do they work less the later they are given?

Benzodiazepines act within minutes by making GABA-A receptors open more often, strengthening the inhibition that a seizure has overwhelmed, which is why guidelines put them first. During a prolonged seizure, however, synaptic GABA-A receptors are pulled into the cell, so there are fewer targets for the drug to act on. In animal models this internalisation tracks the loss of benzodiazepine effect, which is the main explanation for why delay matters and why second-line drugs act on other mechanisms.