Attacking migraine headache from beginning to end
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This issue of Neurology contains four articles describing advances in migraine pharmacology and genetics that are important to practicing neurologists. In the clinical arena, Rapoport et al.1 and Solomon et al.2 report beneficial results in large trials with zolmitriptan, a new orally active antimigraine agent; Ryan et al.3 report improved efficacy using a sumatriptan nasal spray during acute migraine headaches. Both drugs are intended to shorten an attack, reduce the recurrence rate, and treat associated symptoms while avoiding parenteral administration. In a seemingly unrelated report, Gardner et al.4 provide evidence using linkage analysis for a new familial hemiplegic migraine (FHM) locus on chromosome 1q31. This important finding complements a recent discovery showing that a gene encoding the α1A subunit of the P/Q calcium channel is mutated in approximately 50% of families with FHM. Basic and clinical neuroscientists will be excited by the Gardner report because it hints at the possibility of a mutation in the α1E subunit of a related calcium channel. Together, these four reports emphasize that rapid new developments in the biology and treatment of migraine are changing our views about the origins of neurovascular pain syndromes.
The end. Zolmitriptan(S)-4[[3-2[2-(dimethylamino-amino)ethyl-1H-indol-5-yl]methyl]-2-oxazolidinone) is a designer drug that structurally resembles sumatriptan(3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide). Both are agonists that bind with high affinity to 5-HT1D, 5-HT1B, and 5-HT1F receptors. 5-HT1D and 5-HT1F receptors are expressed on trigeminal nerve endings and when occupied by one of these drugs they block neuropeptide release as well as alter neurotransmission in trigeminovascular neurons, possibly within the brainstem as well. 5-HT1B receptors are expressed on vascular smooth muscle cells and mediate vasoconstriction. Both mechanisms may be important for drug action.5 Because of an unfavorable lipid partition coefficient, sumatriptan crosses the blood-brain barrier poorly; therefore, a …
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