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Dimebon (dimebolin) is a perfect example of the black-box nature of drug research for the central nervous system. Any medicinal chemist who looks at its structure would immediately say "CNS", but shrug when asked what specific receptors it might hit. I'd have guessed histamine (correctly), since loratidine used to pay my salary, and I also would have guessed a clutch of 5-HT stuff as well. But it also has activity at AMPA and NMDA glutamate receptors, L-type calcium channels, and more. If you can tell me what it's really doing up there, you shouldn't bother: hang up on me and start calling people with money, because you're ready to take over the CNS therapeutic area for sure.

This blunderbuss is getting a lot of attention these days, since the data for a Phase III trial against Alzheimer's should be available sometime in the spring. The road to that was a strange one. Dimebolin was used for years as an antihistamine in Russia, although I'm not aware if it had any particular reputation for cognitive enhancement in its time as a Soviet allergy pill. It was picked up in screening done during the 1990s at a research institute in the (once secret) military/industrial research city of Chemogolovka Chernogolovka, about two hours from Moscow. It showed effects on learning in rodent models, and gradually advanced to human trials for Alzheimer's. Impressive data came out in 2008, and Medivation, who own the rights to it here, partnered with Pfizer (NYSE:PFE) for development.

Update: the city mentioned above is surely Chernogolovka, but it's interesting that it's appeared many times as Chemogolovka in the English press and literature. I chalk that up to the "rn" looking very much like an "m", and to the mistaken name being semi-plausible in a Stalinist-industrial way, as witness Magnitogorsk. Chernogolovka's much older, though.)

That Bloomberg report I linked to above has a lot of people excited, since there hasn't been a new therapy for Alzheimer's in quite a while (or, arguably, a decent one ever). I don't know what to think, myself. It's absolutely possible that the drug could turn out to have beneficial effects, but it's just as possible that it could miss meeting the high expectations that many investors seem to have for it. (Medivation's stock is up 80% over the last year, for example). A lot of eye-catching numbers from small Phase II trials tend to flatten out in the wider world of Phase III, and if forced, that's the way I'd bet here. (I am most definitely not giving investment advice, though - Alzheimer's drug development is a total crap shoot, and should only be approached with money you can afford to see incinerated).

I hope that Dimebon actually works, though - the world could use something that does. Just don't let anyone convince you that they know how it works, if it makes it through. Unraveling that will take quite a while. . .

Source: Pfizer's New Alzheimer's Drug: A Black Box Indeed