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CNS active Cinchona alkaloid derivatives?


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One for the Brains Trust:
 
Anyone ever seen the Cinchona alkaloid skeleton used as a backbone for CNS therapeutic, psychedelic, or stimulant SAR studies etc?

Just curious as I thought such would have been already explored but I can't find any mention of such explorations in the literature.
 
Surely, one would want to mask the polarity of quinine being an alcohol as the desoxyquinine product, or as keto-analogues for useful CNS activity.
 
Overlaying desoxyquinine with 5-MeO-DMT shows significant potential for 5-HT1/2 agonism with it's structure?

The aromatic-ketoquinine shows significant potential similarity with the known SAR for DAT-inhibiting cathinones?
 
May be an image of text that says 'Desoxyquinidines? H,CK CH CH2 CH3 Hc=o H&C NH Overlay a) desoxyquinine b) 5-MeO-DMT Hyc Agome Agomelatine:MT atine MT receptariS-HT2C amnty Keto-qutrines? Retain cathinone いき BBC.'May be an image of text that says 'Desoxyquinidines? CH2 3C-0 3C Hc- H3C HãO Keto Keto-quinines? Retain a backbone. cathinone like'
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  • 3 weeks later...

I found this on quinines interaction with serotonin (from 10.1038/srep03618):

 

> Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells.

 

It's a good option to reduce excess serotonin which isn't desirable for various reasons.

 

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