OK - I was interested to discover that 3-ring nitrobenzodiazepines act as hypnotics because of their a1 affinity and the to now unnoticed effect that they are serotonin releasing agents. Now, the 4-ring (triazolo) benzodiazepines have little to no a1 affinity thus starting with alprazolam. simply swapping the 8-Cl for an 8-nitro produces prompt antidepressant (within 60 minutes) effects. I have tested the nitro analogue of alprazolam ($629/Kg) and the nitro analogue of pyrazolam. I do not know if a '2 -F or '2-Cl increases the serotonin releasing effects BUT as far as I can tell, such compounds have a huge TI and the nitro analogue of pyrazolam (pynazolam) is excreted unchanged.
If people are unaware, nitro benzodiazepines are most commonly used in successful suicide attempts which I posit is because generally the aromatic nitro is reduced to the aromatic amine. This is just a theory but I do think we have a new medicine waiting to be used. The TI of pynazolam is HUGE, I mean >500 (ran out of material and don't like killing animals) in animal models. I think it was Labrat who said 'don't send a rat to do a mans job' but I do not have a death wish.
I do hope someone has the chance to study this more. It would make an excellent pHd thesis, I suggest. If you want notes, boy, do I have notes.
If people are unaware, nitro benzodiazepines are most commonly used in successful suicide attempts which I posit is because generally the aromatic nitro is reduced to the aromatic amine. This is just a theory but I do think we have a new medicine waiting to be used. The TI of pynazolam is HUGE, I mean >500 (ran out of material and don't like killing animals) in animal models. I think it was Labrat who said 'don't send a rat to do a mans job' but I do not have a death wish.
I do hope someone has the chance to study this more. It would make an excellent pHd thesis, I suggest. If you want notes, boy, do I have notes.