Pharmacodynamics of arylcylohexylamines: Sedation

[QtHedgehog]

Hello!

I was wondering whether we had a pharmacological explanation concerning sedation of certain arylcyclohexylamines compared to other ones. I wasn't able to find anything on this subject, but I noticed that 3-MeO-PCP, which is stimulating and manic, has affinity for the σ1 receptors, while ketamine, which is sedative, hasn't; could it explain the stimulating properties?

Any idea for an explanation is very welcome!
Thanks a lot

 

[Chris Timothy]

Sigma1 could contribute, but it's not that clear where it falls on the upper/downer spectrum. Similarly, ketamine's effect on MOR seem a mixed bag as well.

On the other hand, ketamine quite clearly inhibits noradrenalin, one of the body's major uppers.

 

[negrogesic]

Aside from the disconnective effects of glutamate inhibition there are other things bringing about sedation, like through anticholinergic means etc.

 

[Chris Timothy]

Huh, yeah the anticholinergic effect is much stronger. I glanced over it because I thought ketamine and deliriants can't have much in common. But that's conflating muscarinic receptors with nicotinic receptors.