Posted by Flash (18.104.22.168) on June 12, 2001 at 02:42:57:
In Reply to: Ergot posted by Bob P on June 11, 2001 at 12:39:13:
Hofmann was working with Ergot based compounds. They already new about Ergotamine which was first synthisized in 1918 (I think from memory). It was already known that Ergotamine was useful in treating migraine since it was a powerful vascular constrictor.
Hofmann first synthesisd what was essentially the nucleus of Ergotamine. This turned out the be LSD. LSD had many interesting effects, none more so than it's strong hallucinogenic properties. It was also a very weak vascular constrictor and turned out to be a good Serotonin antagonist of 2 types of Serotonin receptor. I think this means it binds to two particular types of serotonin receptor, blocking the from reaching them. They realised that this would be useful in the treatment of migraine since it was known that excess Serotonin accompanied each migraine attack, and that one of the receptors that LSD bound to was specifically implicated in migraine. Hofmann then went on to produce an even more powerful Serotonin antagonist (from memory I think something like 20x as powerful as LSD) by doctoring LSD. This substance was christened Methysergide. It lacked most of the hallucinogenic effects of LSD, but it did bind specifically to the Serotonin receptor implicated in Migraine. Most migraine research was then focused on Methysergide.
Since I have first hand experience of using LSD to treat CH, I am of the belief that they threw the baby out with the bath water. I don't think it's vascular constriction properties are important. I think that the fact it binds to more Serotonin receptors than Methysergide might be important since those particular receptors that LSD binds to and Methysergide doesn't are now also thought to be implicated in vascular headaches. Interestingly there are other drugs available that bind specifically to this receptor, and correct me if I'm wrong but they are triptans (such as Imitrex) although the effect they have on the receptor is slightly different. LSD is the only substance that binds to both these particualr receptors though. This might be why it is hallucinogenic!!!
Sorry if this information is sketchy, but I'm sure that someone can confirm it more scientifically if they try. I couldn't be arsed going back and trawling through it all again. The key document you'll need is easily obtainable on the Net - "LSD: My Problem Child" by Albert Hofmann. You'll also need a list of drugs used to treat vascular headaches and the particualr Serotonin receptors that they bind to.
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