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Sunday, April 16, 2006

Designer Drink: Alcoholic without alcohol

It is now a thought experiment: How to design a molecule that acts on the brain as alcohol does, but, the molecule will not effect the human with sickness, nausea, headaches, or a hang-over? The molecule (or pill, really) will give the taker, that is, druggie (let's be honest) his craved high but without the nasty side effects.

New Scientist reports:

Alcohol exerts its effects on the brain mainly by latching onto signalling molecules called GABA-A receptors. There are dozens of subtypes of these, some of which are associated with specific effects of alcohol. Memory loss, for example, seems to occur because alcohol binds to a subtype in the hippocampus called alpha-5. Nutt [psychopharmacologist David Nutt of the University of Bristol in the UK] says it would be possible to design molecules that bind strongly to the good subtypes but more weakly to the bad ones.

In fact such "partial agonists" of GABA-A receptors already exist in the form of bretazenil and pagoclone, which were developed as anti-anxiety drugs but never commercialised. These molecules also have the advantage of being instantly reversible by the drug flumazenil, which is used as an antidote to overdoses of tranquillisers such as Valium. Alcohol also inhibits NMDA receptors, which are part of a general excitatory signalling circuit, so a second ingredient of the alcohol substitute would be an NMDA antagonist such as dizoclipine, originally developed as a drug for stroke.

So, now we have science, at the thought level to be sure, looking at how to develop designer drugs for alcohol replacement. Somehow this just strikes me to be a drug pusher's dream. We have LSD, heroin, pot, cocaine, and meth. Some natural, some not. Now, someone seeks to design an alcohol-effects-based drug. Alternatively, if such a drug would help alcoholics and others to avoid the problems associated with drinking, then maybe there is something here. Hard for me to tell.

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