Figure 2

Main potential targets of currently utilized preventive drugs and those under-investigation for migraine. The mechanisms mediating CSD inhibition by several migraine preventive drugs are not completely understood. However, it is believed that this inhibitory action is exerted by influencing ion channels and neurotransmission. In particular, topiramate and valproate are believed to exert their antagonizing effects on CSD by blocking Na⁺ channels, inhibiting glutamatergic transmission and increasing GABaergic transmission. Topiramate, but not valproate, can also block L-type Ca²⁺ channels. Lamotrigine has a marked suppressive effect on CSD, which may be due to its selective action on Na⁺ channels. Furthermore, gabapentin is able to modulate the activities of P/Q- and, to a lesser extent, N-type high voltage-activated channels located presynaptically at the cortical level and controls the neurotransmitter release, in particular that of glutamate. This effect and the modulation of GABA-mediated transmission might explain CSD inhibition by gabapentin. Magnesium exerts an inhibitory effect on CSD by interfering with NMDA receptor function and reducing glutamatergic transmission as well as regulating glutamate uptake by astrocytes and modulating NO system in the cortex. The blockage of L-type Ca²⁺ channels may also account for the inhibitory effects of flunarizine on CSD (not shown). The novel benzopyran compound tonabersat seems to inhibit CSD in experimental models and has shown some efficacy in the prophylactic treatment of MwA. It is not known if tonabersat acts on gap-junctions in CNS, as it has already been demonstrated for trigeminal ganglion. CSD inhibition can also be achieved by CGRP-R blockage due to CGRP antagonists, such as olcegepant. This class of drugs might exert its inhibitory effects at both cortical neuronal and cerebrovascular levels.