Have any new short-to-mid term benzos 7-9 hrs appeared on the scene within last two years?
There are literally THOUSANDS.
Now some couldn't technically be controlled as benzodiazepines. Things such as brotizolam are not technically benzodiazepines but just in case thiophene rings are also explicitly covered, zapizolam, zolazepam and so forth show that many 5 and 6-membered hetrocyclic rings work. I would be surprised if the furan analogue of brotizolam wasn't active, for example.
Heck, clazopam may suggest that rigid analogues are also active. With the latter, to be more certain I would go for adding a triazolo ring or similar because we pretty much know that etodimate (sold as 'Space Oil' for vapes in Hong Kong) is also part of the scaffold of some of the most potent benzodiazepines. Those developed in the 90s and 00s by Professor James T. Cook (et al) at the Milwaukee Institute of Drug Discovery. Clearly that extra bit of scaffold increases affinity (although they DID find a far less labile bioisostere than the ester found in etodimate) and derivatives with a
para halide e.g. a -Cl in the same spot as the -Cl in diazepam are sold as research ligands so I think there is quite a large overlap.
I've mentioned it before but I am surprised that since 7OHM appears legal in some states on the basis that it's 'natural' (even though we know it's made from mitragynine, an item of international commerse), surely someone could synthesize kavain and similarly claim it's just Kava extract?
I don't know very much about US law but I do know that people were harmed by 'farmed' kava in which the entire plant was used whereas traditionally only certain parts are harvested and you guessed it, the parts of the plant typically discarded contained hepatotoxins (chalcones). So I don't know if Kava is already legally controlled.
I know researchers are currently looking at various actives within kava but all are making it abundently clear that they extract and seperate the various lactones which does suggest that the regulations surrounding a natural product are easier to work within that if a synthetic was used.
But whatever the detail, sooner or later someone will offer something chemically unrelated to the benzodiazepines.
The French typically use etifoxine but I was gifted a full set of 'Annual Report of Medicinal Chemistry' and several other classes looked promising BUT because chlorodiazepoxide was a few years ahead of the alternatives and Leo Sternbach had worked out the QSAR of scores if not hundreds of analogues, any competitor would have to have shown a significant clinical advantage and because benzodiazepines were so incredibly non-toxic compared with the medications they replaced, I strongly suspect nobody felt a clinicial advantage COULD be shown. Don't forget, by the mid 60s benzodiazepines were heralded as 'miracle drugs' offering so many advantages with seemingly no risks.
But as I have said before, if a person becomes physically dependent on a benzodiazepines, abrupt cessation can and does kill.
