Yes Don't miss it!
It'll be interesting to hear what he's got to say on physostigmine, as I'm sure there will be mention of the fact that the answer was there all along, yet no-one had thought it important enough to look a bit deeper.
This says something about everything. From allocation of government research funds, to pharmaceutical companies offering to find an answer[NOT]. It even spreads to doctors and academics many of whom
should have been concerned enough with G related hospital admissions to have searched to find a solution. A solution which incidentally, was waving a "published reference hand" for all to see. Well thankfully there is a concerned Dr or 2. drplatapus's team did the searching and came up with something published shortly after GHB was first synthesized.
Despite recent media hysteria highlighting the numbers of admissions to emergency, and the expected responses that would create, it would again seem this is simply another example where the coalface workers have had to provide the answer. Was it that no-one else in the right position could be bothered?
While I don't wish to in anyway understate the achievements of drplatapus and his team, the fact remains that the basic information on Physostigmine being used for G-OD, was already in existence. Some Bluelighters are good reference hunters
but if it weren't for the fact that a team of medical researchers made the find, it may have been a discovery in vain, as it seems few ears of significance were listening - well, they certainly weren't looking.
To doctors who may remember once prescribing it for glaucoma or as antidote to insecticide or TCA poisonings, physostigmine would at first seem an odd choice for treating a GHB coma, as it's typically a drug used to block actions of drugs like scopolamine and atropine, and so works primarily on ACh (muscarinic) receptors.
It was used as an antidote for tricyclics where it exerted neuroprotective effects on areas of the brain affected by these drugs. Goodman and Gilman (6th Ed) lists Physostigmine as
the only reversible anticolinesterase with appreciable capacity to cross the blood brain barrier to exert central actions.
[This is due to physostigmine being a tertiary amine, as opposed to many other agonists of this class which are quaternary amines and don't get through]
The danger - in case anyone thinks self medicating will be the go - is that physostigmine is itself a powerful poison, capable of causing seizure itself. So leave the administration to someone who hasn't already made the mistake of over-dosing.
Here's a bit on the history and pharmacology of physostigmine. It comes from the Calabar bean, a perennial in tropical Africa. The bean was used by tribes of West Africa as an "ordeal poison" for witch-craft. Work done by Daniell in 1840 established some of it's pharmacological properties. in 1864 a pure alkaloid was extracted and named both
Physostigmine and eserine by different researchers. By 1880 it was being employed in the treatment of glaucoma. Physostigmine remained one (the least toxic) of the few known reversible anticholinesterase (AChE) inhibiters. Non-reversible AChE inhibiters were unknown until around world war II when the nerve gas and pesticide research resulted in the nasty carbamyl esters and organophosphorous compounds.
The reason physostigmine isn't used today so much is that better replacements were found for most of it's uses. It also found uses as a tricyclic antidepressant antidote. The modes of action -from what I've been able to discover - aren't well known, but I'd be interested to see what lead to it's discovery as a GHB antidote.
Interesting stuff. Program your schedule for Thursday, 8:00pm ABC.
Physostigmine
