Piperidine-4-sulfonic acid
Piperidine-4-sulfonic acid is a synthetic GABAA receptor agonist and a cyclized analogue of the inhibitory neurotransmitter γ-aminobutyric acid.
Pharmacology
The drug is a potent and selective GABAA receptor partial agonist. It shows functional selectivity at GABAA receptors of different α subunit compositions, with high activational efficacy at GABAA receptors containing α2, α3, and α5 subunits and low efficacy at GABAA receptors containing α1, α4, and α6 subunits. As such, it is said to activate the former receptors but to essentially block the latter receptors. This is in contrast to other GABAA receptor agonists like isoguvacine and gaboxadol, which show broadly higher activational efficacies at GABAA receptors of different subunit compositions. In addition to its GABAA receptor partial agonism, P4S is described as a moderately potent GABAA-ρ receptor antagonist, a property that it shares with gaboxadol. Unlike certain related compounds like muscimol, P4S is not a GABA reuptake inhibitor.P4S is a highly charged zwitterion. In contrast to other related GABAA receptor agonists like muscimol and gaboxadol, P4S is unable to cross the blood–brain barrier and hence is [peripherally binding selectivity|selective drug|peripherally selective]. As a result of this, animal behavioral studies with this compound have not been possible.