Gabapentinoids

Ligands at the α2δ auxiliary subunit of voltage-gated calcium channels, where they reduce the release of excitatory neurotransmitters. Despite the names, gabapentin and pregabalin do not act at GABA receptors at all. Phenibut is the exception that makes the family read oddly: it binds α2δ and is also a GABA-B agonist, which is why it is the sedative and anxiolytic member, and why its dependence and withdrawal are heavier and longer than the others'.

Absorption is the practical difference between the medicines. Gabapentin's uptake saturates, so taking more does not mean proportionally more absorbed, while pregabalin's does not and behaves predictably. Alone these depress breathing weakly; added to an opioid they raise the risk of a fatal overdose, and that combination is the main reason the class is on a harm-reduction site. Coming off phenibut in particular can require a long taper.