Migraine is a primary headache disorder with an unknown pathophysiology. The growing evidence in recent
years indicates migraine being a brain disorder, a sensory dysmodulation, and a system failure of normal sensory
processing of the brainstem that involves the vascular tone and pain. At the moment, triptan family and NSAIDs are the
first choice drugs for the treatment of acute migraine. There are several prophylactic drugs including the antiepileptic
drugs (AEDs), betablockers, and Ca2+ channel blockers that are used for the treatment of migraine. Although many drugs
including the triptans, NSAIDs, and others target the peripheral sites of activation, several novel drugs are being
developed to target neural sites of action in the central nervous system (CNS). The first trigeminal synapses in the brain
stem as well as the ascending and descending pathways and higher brain centers are involved in the transmission of pain
and therefore be the main targets of several drugs some of which are in clinical trials. Central sensitization may also
aggravate the headache and some drugs tend to alleviate pain by targeting neurotransmitters, receptors, or signalling
molecules involved in this phenomenon. This article discusses the CNS acting novel drugs and those that are currently in
use for the treatment of migraine.
Keywords: Migraine treatment, CNS acting drugs, trigeminal nucleus, central nervous system (CNS), NSAIDs, anticociceptive fibers, neuronal hyperexcitability, brainstem.
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