These are my thoughts on benzos based on experience and educated guessing. Please feel free to critique.
- R⁷ can be a nitro group or a halogen (bromine or chlorine). It seems bromine is the "heaviest" (most hypnotic?), while nitrogen is most recreational / euphoric.
- R²' is an optional substitute, but when present, usually a halogen and it increases the potency.
- R² is a double-bonded oxygen (ketone), except for with triazolodiazepines which fuse R¹ and R² together with a nitrogen to form a 1,2,4-triazole ring.
- R¹ can be nothing or a methyl group, again though with the exception of triazolodiazepines like alprazolam.
- On the triazole ring, the methyl group can be removed cutting potency by 50% but increasing the duration. E.g.: compare etizolam to metizolam, the latter is half the potency of the former but nearly double in terms of duration.
I believe flunitrazolam maxes out euphoric traits and potency. Indeed, it's active at 0.1 mg. The trouble seems to be it's so very amnesic, it's recreational potential is compromised by this trait. This makes sense though considering flunitrazepam is the infamous date-rape drug, Rohypnol (which, fun fact: has never been legally sold in the U.S.).
Of course there are other substitutions possible, such as 3-methylbenzodiazepines, which are metabolites of other benzos. For example oxazepam is a metabolite of diazepam. It is also possible to replace the phenyl ring with a pyridine one, as seen in pyrazolam. This seems to be of similar potency as a 2-chlorophenyl group, but causes the substance to be active at different subreceptors.
Another possibility is going from benzodiazepines to thienodiazepines. Here the upper phenyl ring is replaced by thiophene. This also increases the potency a bit. An example is etizolam:
The most potent possible benzodiazepine derivative might therefore be something like Flubrotizolam (Flu = R2' fluorine, bro = R7 bromine, ti = thiophene, zolam = triazolo). However, I've never tasted this compound; can anyone comment?
