paracelsius
Bluelighter
- Joined
- Mar 11, 2020
- Messages
- 197
Consider the most potent NMDA antagonist known to man: MK801 aka Dizocilpine aka Neurogard.
More like the LSD of dissociatives except it has insane 3-days+ half-life!. Removing the quaternary carbon bridge between the 2 phenyl rings lead to lefetamine, diphenidine ..etc type of NMDA antagonists, ring-opened versions of MK801. Not quite as active but still decent NMDA antagonists with reduced cholinergic and reduced half-life. Now, instead of removing the quaternary carbon, you remove the bond bewteen the tertiary carbon and the phenyl ring (to the right), you get
1-methyl-1-phenyl-dihydro-isoquinoline aka FR-115427 aka FR-427. Now this compound is exactly (not almost) exactly like pcp: susbtitute for pcp (99.6%) in pcp-trained rats. In other words, rats can't make difference with pcp 99.6% of the time which is pretty much to say never. A little bit more potent than pcp (1.4x the potency of pcp @nmdar displacement of TCP which means it binds same site as diarylcyclohexylamines) and probably has similar half life as pcp (I dont know abt the T1/2 tho just guess). Which is the reason development of this compound as anticonvulsant was stopped since it was expected to have same "hallucinogenic side-effects profile as pcp" according to the authors so it was never tested in humans afaict. Pretty straighforward one step synthesis from acetophenone and PEA. Not the best of yields, pictect-spengler rx work best with activated PEAs (like p-methoxy PEA..etc) or with aldehydes instead of ketones. I bet the methoxy analogs (MeO on one of the 2 phenyl rings) would probably be more potent!. It doesnt look like anything scheduled since it is an isoquinoline, not a diarylcyclo(alkyl)amine or an isoquinuclidine like MK801, but correct me if I am wrong.
More like the LSD of dissociatives except it has insane 3-days+ half-life!. Removing the quaternary carbon bridge between the 2 phenyl rings lead to lefetamine, diphenidine ..etc type of NMDA antagonists, ring-opened versions of MK801. Not quite as active but still decent NMDA antagonists with reduced cholinergic and reduced half-life. Now, instead of removing the quaternary carbon, you remove the bond bewteen the tertiary carbon and the phenyl ring (to the right), you get
1-methyl-1-phenyl-dihydro-isoquinoline aka FR-115427 aka FR-427. Now this compound is exactly (not almost) exactly like pcp: susbtitute for pcp (99.6%) in pcp-trained rats. In other words, rats can't make difference with pcp 99.6% of the time which is pretty much to say never. A little bit more potent than pcp (1.4x the potency of pcp @nmdar displacement of TCP which means it binds same site as diarylcyclohexylamines) and probably has similar half life as pcp (I dont know abt the T1/2 tho just guess). Which is the reason development of this compound as anticonvulsant was stopped since it was expected to have same "hallucinogenic side-effects profile as pcp" according to the authors so it was never tested in humans afaict. Pretty straighforward one step synthesis from acetophenone and PEA. Not the best of yields, pictect-spengler rx work best with activated PEAs (like p-methoxy PEA..etc) or with aldehydes instead of ketones. I bet the methoxy analogs (MeO on one of the 2 phenyl rings) would probably be more potent!. It doesnt look like anything scheduled since it is an isoquinoline, not a diarylcyclo(alkyl)amine or an isoquinuclidine like MK801, but correct me if I am wrong.
