Cycloalkylamides of d-Lysergic Acid

[trade_om]

Hello.
Ive been going through patents and found this one dating back from 1959. It describes how to synthesis cycloalkylamides of d-Lysergic Acid. It also states that cycloalkylamides of the acid have more anti-serotonin activity then lsd-25(5 fold).

Patent GB816273

[Lilienthal]

That is interesting historically interesting. It was later found that hallucinogens act as  serotonin-mimetics and not as anti-serotonergics at a certain subtype of serotonin receptors, i.e. they are agonists at the 5-HT2A receptor.  

[Nicodem]

Yes, but if they are partial agonists like LSD, they actually block the effect of serotonin in tissue preparations. They occupy the receptor sites but have a lower activity than serotonin itself. Hence LSD was said to have antiserotonin activity as it actually has but only relatively to serotonin. But now we are in the best years of neurochemistry and like Lily says, it's historically interesting.

[7is]

They don't have LSD-like effects according to Nichols:

Votava et al (1958) prepared a series of cycloalkyl monosubstituted amides in a series from aminocyclopropane
(a three-carbon ring system) through aminocycloheptane (a seven-carbon ring system). The aminocyclobutane and
aminocylopentane cycloalkylamides, shown above, gave antiserotonin effects in a rat intestine preparation that were
30% greater than LSD itself, but the compounds did not have LSD-like effects in man.

http://www.heffter.org/review/Review2/chap6.pdf