Benzodiazepines

Positive allosteric modulators at the benzodiazepine site of GABA-A: they increase the effect of the GABA already being released rather than opening the channel themselves, which gives them a ceiling and is why they are more survivable alone than barbiturates. That ceiling is irrelevant in combination — with opioids, alcohol or any other depressant the respiratory depression simply adds.

Onset, duration and active metabolites vary across the family more than anything else does. Diazepam leaves long-lived active metabolites behind; alprazolam is short and rebounds sharply; the designer members — clonazolam, flubromazolam, flualprazolam, bromazolam — are active at amounts small enough that no home preparation mixes them evenly, which is how one pressed tablet or blotter turns out far stronger than the next. Amnesia is characteristic rather than incidental. Flumazenil reverses the site but can precipitate seizures, and withdrawal after sustained use needs a taper for the same reason.