Valproate has been shown to be an effective prophylactic treatment in
migraine. Investigation of the mechanism of its antimigraine action is
difficult due to the broad range of its biochemical effects and the c
omplex nature of migraine pathophysiology. Valproate increases brain G
ABA levels and, in doing so, may suppress migraine-related events in t
he cortex, perivascular parasympathetics or trigeminal nucleus caudali
s. There is experimental evidence that it suppresses neurogenic inflam
mation and directly attenuates nociceptive neurotransmission. In addit
ion, valproate reportedly alters levels of excitatory and inhibitory n
eurotransmitters and exerts direct effects on neuronal membranes in vi
tro. Valproate's observed effect may ultimately result from a combinat
ion of actions at different loci.