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'Antidotes' for OD situations.

There are actually some species of mushrooms, like the Omphalotus olearius, which contain enough muscarine to cause a cholinergic poisoning (increased salivation, poor vision, slow heart rate etc.) if ingested. Nerve gases cause similar symptoms by inhibiting the breakdown of acetylcholine in synapses.
 
A muscimol overdose would most obviously be treated with a GABA antagonist. That being rather dangerous, and flumazenil being relatively safe by comparison, makes a bit more sense.

It might not work, since flumazenil is binding to another site, but it does decrease GABA's effect, so it should conceivably decrease muscimol's effect as well. I think.
 
^ A benzodiazepine inverse agonist like Ro15-4513 would decrease GABA's effect even more. Actually so much that when administered to someone, they cause symptoms similar to benzo withdrawal even in people who are not dependent on benzos.
 
thanks for letting me know what inverse agonists are... ;)

doesn't seem important since the goal is to prevent problems, not cause new ones through opposite mechanisms.
 
polymath said:
^ A benzodiazepine inverse agonist like Ro15-4513 would decrease GABA's effect even more. Actually so much that when administered to someone, they cause symptoms similar to benzo withdrawal even in people who are not dependent on benzos.
Click to expand...

I was about to suggest a partial agonist like imidazenil.

but if muscimol binds to a different site... wouldn't you need a ligand that binds to the main site?
 
Not necessarily. Benzos bind to a different site on the same receptor pore, but they don't have intrinsic activity: they have their effect by enhancing GABA. Benzo antagonists decrease GABA's activity (correct me if I'm wrong - if neutral benzo antagonists are truly neutral perhaps an inverse agonist might actually be needed, but I doubt this since neutral antagonists do produce seizures and such) so they should also reduce muscimol's activity.

However! It might not be that simple.

1) could a different agonist like muscimol activate a different pathway similar to the way LSD activates pathways that 5HT doesn't? Obviously GABA receptors aren't GPCR's, though.

2) agonist distribution. muscimol is distributed to parts of the brain that the antagonist isn't (since it obviously produces effects very different from GABA itself), the antagonist might still be ineffective.

I like 1) more, but 2) seems more likely.
 
The compound bicuculline blocks GABA-A receptors, binding to the same site as GABA itself. It causes convulsions like pentetrazol and other such drugs.

If I have understood correctly, flumazenil and other benzo antagonists have caused convulsions only when given in too large doses as a benzo antidote to benzo-dependent people, and withdrawal has precipitated. Similarly a non-opiate-dependent person can take a huge dose of naloxone/naltrexone without feeling bad...
 
Not exactly. Flumazenil can cause seizures in benzodiazepine naive people as well, though it's not a really major risk, I wouldn't discount it, either. I believe it was Ott who published a "trip report"of his experience with Naltrexone in the Journal of Psychoactive Drugs. Nothing about the experience- dependent or not- seems positive, though that seems to moderate with chronic administration.
 
I think bupe would be effective in cases of opioid OD, but I'd like some backing on that. Also, is it possible to OD on bupe alone? I've read respiratory depression cuts off at 2mg.
 
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