News from the AAN meeting:

For a large number of migraine sufferers (myself included) and neurologists (again, myself included) the development of the triptans for acute migraine was something of a miracle. But there are some migraines (and some migraineurs) that are not helped by these wonder drugs. That's why it is so encouraging that there are some fundamentally different medications coming down the pipeline.

Just to review, the triptans work by stimulating the 5-HT 1B/1D receptors. Sumatriptan (imitrex) was the first one developed. I use rizatriptan (Maxalt) for my own migraines. Others include zolmitriptan (Zomig) (I prescribe this a lot at my VA hospital because it is the only triptan pill on the formulary), frovatriptan (Frova), naratriptan (Amerge), almotriptan (Axert), and eletriptan (Relpax).

Here are some new treatment mechanisms that are getting close to the stage at which actual drugs may soon be approved (say in a year or two):

CGRP (calcitonin gene-related peptide) Antagonists. One of these, telcagepant, is actually in phase III trials right now. That means it is very close to the end of the testing process (again, a year or two).

Vanilloid receptor antagonists. Some of the vanilloid receptors are located on the same neurons as are the CGRP receptors. The vanilloid receptor antagonists seem to be less well studied and thus further from clinical readiness.

I do not have an in depth understanding of the mechanisms of either the CGRP or the Vanilloid receptors, but, apparently, blocking either the CGRP or the vanilloid receptors antagonizes the dilation of blood vessels located on the dura (a membrane surrounding the brain) by interfering with the action of capsacin (which is independently known to be a pain inducing substance). So this seems to make sense. The extra good part of both the CGRP and the Vanilloid story is that neither of these appear to induce vasoconstriction, which is sometimes a problem with the triptans (but it seems to me that blocking dilation of the dural blood vessels is somewhat akin to vasoconstriction, but I guess it is not direct vasoconstriction).

There is also a new type of serotonin agonist being studied. The new type activates the 1F receptors rather than the 1B and/or 1D receptors. The first prototype studied had too many side effects and was abandoned. But other such compounds are being developed.

Finally, some scientists are working on drugs that block nitric oxide synthase. But work on these is not as far along as work on the others. Frankly, I would think this could be dangerous because nitric oxide synthase is very beneficial. It is one of the good guys in helping to relieve cardiovascular and cerebrovascular constriction. I would be scared to block my nitric oxide synthase. But perhaps some smart person will find a safe way of doing it.