Piperidine-4-sulfonic acid (P4S) is a synthetic GABA<sub>A</sub> receptor agonist and a cyclized analogue of the inhibitory neurotransmitter ó-aminobutyric acid (GABA).
The drug is a potent and selective GABA<sub>A</sub> receptor partial agonist. It shows functional selectivity at GABA<sub>A</sub> receptors of different ñ subunit compositions, with high activational efficacy at GABA<sub>A</sub> receptors containing ñ<sub>2</sub>, ñ<sub>3</sub>, and ñ<sub>5</sub> subunits ( = 75âÂÂ96%) and low efficacy at GABA<sub>A</sub> receptors containing ñ<sub>1</sub>, ñ<sub>4</sub>, and ñ<sub>6</sub> subunits ( = 7.2âÂÂ21%). As such, it is said to activate the former receptors but to essentially block the latter receptors. This is in contrast to other GABA<sub>A</sub> receptor agonists like isoguvacine and gaboxadol (THIP), which show broadly higher activational efficacies at GABA<sub>A</sub> receptors of different subunit compositions. In addition to its GABA<sub>A</sub> receptor partial agonism, P4S is described as a moderately potent GABA<sub>A</sub>-àreceptor 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 GABA<sub>A</sub> receptor agonists like muscimol and gaboxadol, P4S is unable to cross the bloodâÂÂbrain barrier and hence is peripherally selective. As a result of this, animal behavioral studies with this compound have not been possible.
P4S was first described in the scientific literature by Povl Krogsgaard-Larsen and colleagues by 1979. Along with gaboxadol, it was one of the first selective GABA<sub>A</sub> receptor agonists to be identified.