SH-I-048A ( Benzodiazepine Super Agonist ) ?

[MedicinalUser247]

SH-I-048A (SH-i-048A) is a benzodiazepine derivative related in structure to compounds such as flubromazepam and meclonazepam. SH-I-048A is described as a non subtype selective superagonist at the benzodiazepine site of the GABAA receptors with a binding affinity of 0.77 nM at the α1 subtype, 0.17 nM at α2, 0.38 nM at α3 and 0.11 nM at α5. It has been used to study the functional differences between the different subtypes of the GABAA receptor. This sounds like a Drug I'd love to try. What are your thoughts on SH-I-048A ?

 

[Deleted member 170540]

Sounds like it potentially has an overdose risk similar to barbiturates and methaqualone, even when not combined with other CNS depressants.

 

[4DQSAR]

The affinity itself does not describe what is and what is not a superagonist. It's the effaciacy. If the effacacy of an exogenous ligand is higher than the endogenous ligand(s).

A ligand can haw low affinity but still demonstate superagonist activity when it does form the ligand-receptor complex.

Tianeptine, tapentadol and etonitazine are superagonists and possibly both ODMT and 7OHM as well. Some are potent, some are not.

But the usual way we discover that a novel opioid IS a superagonist is when substitution therapy is undertaken. Typically no dose of methadone or buprenorphine will halt the AWS.

 

[4DQSAR]

BTW the compound you specified is chiral - what is the affinity data for the other isomer?

Because if it's far lower, the raecemic product may not demonstate superagonism.