The basic CNS neuropharmacology of
naratriptan is reviewed here.
Naratriptan is a second-generation
triptan antimigraine
drug, developed at a time when CNS activity was thought not to be relevant to its
therapeutic effect in
migraine. It was, however, developed to be a more
lipid-soluble, more readily absorbed and less readily metabolized variant on preexisting
triptans and these variations conferred on it a higher CNS profile.
Naratriptan is a 5-HT(1B/1D) receptor agonist with a highly selective action on
migraine pain and
nausea, without significant effect on other
pain or even other trigeminal
pain. Probable sites of therapeutic action of
naratriptan include any or all of: the cranial vasculature; the peripheral terminations of trigeminovascular sensory nerves; the first-order synapses of the trigeminovascular sensory system; the descending
pain control system; and the nuclei of the thalamus.
Naratriptan may prevent painful dilatation of intracranial vessels or reverse such painful dilatation.
Naratriptan can prevent the release of sensory
peptides and inhibit painful neurogenic vasodilatation of intracranial blood vessels. At the first order synapse of the trigeminal sensory system,
naratriptan can selectively suppress neurotransmission from sensory fibers from dural and vascular tissue, while sparing transmission from other trigeminal fibers, probably through inhibition of
neuropeptide transmitter release. In the periaqueductal gray matter and in the nucleus raphe magnus,
naratriptan selectively activates inhibitory neurons which project to the trigeminal nucleus and spinal cord and which exert inhibitory influences on trigeminovascular sensory input.
Naratriptan has also a
therapeutic effect on the
nausea of
migraine, possibly exerting its action at the level of the nucleus tractus solitarius via the same mechanisms by which it inhibits trigeminovascular nociceptive input. The incidence of
naratriptan-induced adverse effects in the CNS is low and it is not an
analgesic for
pain other than that of
vascular headache. In patients receiving selective
serotonin uptake inhibitors (
SSRIs)
naratriptan may cause
serotonin syndrome-like behavioral side effects. The mechanism of action involved in the production of behavioral and other CNS side effects of
naratriptan is unknown.