British 2C-x Study

[MachineGunBallad]

http://www.nature.com/bjp/journal/v141/n7/full/0705722a.html

I am not familiar with neurochemistry and its jargon, but for those who are, would it be possible to translate the significance of this study? The impression I get is that there is growing evidence, which this study seems to contribute to, that psychotropic substances are partially serotin antagonists rather than agonists, as is commonly believed. What's the importance of this in terms of neurotoxicity of these chemicals?

 

[Dr.Heckyll]

Hmm. This seems to be nonsense putting everything that's known about hallucinogens upside down. To really make a point they should have tested some compound which have previously been show tom be 5-HT2A antagonist. All they prove is that receptor expressed in Xenopus laevis show erratic behaviour. However, there really is a discrepancy between 5-HT2A affinity/efficiacy and in vivo hallucinogenic activity. Just look at NIchols' studies of lysergic acid amides. The (2S,4S)-2,4-dimethylazetidine has less than half the receptor affinity (8.3 nM) compared to LSD (3.5 nM), but twice the potency in vivo (rats). Who knows, maybe the hallucinogenic activity is really caused but a receptor other than 5-HT2A?

 

[nuke]

^^ I would more wager that it has something to do with both 5ht2a and c, their respective locations in the brain, and also with the g-protein coupling that happens post-binding.

I don't think the study says anything we don't already know about psychedelics, that they're both selective 5ht2a partial/full agonists and antagonists, depending on the cell and its location.

 

[Beenhead]

Is thorazine as effective for abortion of expereince on 2C-x as it is for LSD-Psilocybin?

 

[Ernestrome]

Is thorazine as effective for abortion of expereince on 2C-x as it is for LSD-Psilocybin?

Do you consider thorazine to be the most effective way of ending LSD or shroom trips?

 

[Dondante]

Hmm. This seems to be nonsense putting everything that's known about hallucinogens upside down. To really make a point they should have tested some compound which have previously been show tom be 5-HT2A antagonist. All they prove is that receptor expressed in Xenopus laevis show erratic behaviour. However, there really is a discrepancy between 5-HT2A affinity/efficiacy and in vivo hallucinogenic activity. Just look at NIchols' studies of lysergic acid amides. The (2S,4S)-2,4-dimethylazetidine has less than half the receptor affinity (8.3 nM) compared to LSD (3.5 nM), but twice the potency in vivo (rats). Who knows, maybe the hallucinogenic activity is really caused but a receptor other than 5-HT2A?

According to the paper on (2S,4S)-2,4-dimethylazetidine, it stimulated twice the PI turnover of LSD. It has higher intrinsic activity at the 5HT2A receptor. I thought that was the key to its increased potency.