Thio-4-PIOL, also known as 5-(piperidin-4-yl)isothiazol-3-ol, is a GABA<sub>A</sub> receptor weak partial agonist or antagonist related to 4-PIOL.
The drug acts as a weak partial agonist or antagonist of the GABA<sub>A</sub> receptor, with varying efficacy depending on the receptor complex's specific subunit composition. It shows values of up to approximately 30% at ñ<sub>5</sub>ò<sub>3</sub>ó<sub>2S</sub>, ñ<sub>4</sub>ò<sub>3</sub>ô, and ñ<sub>6</sub>ò<sub>3</sub>ô GABA<sub>A</sub> receptors, 4 to 12% at ñ<sub>5</sub>ò<sub>2</sub>ó<sub>2S</sub>, ñ<sub>4</sub>ò<sub>2</sub>ô, and ñ<sub>6</sub>ò<sub>2</sub>ô GABA<sub>A</sub> receptors, and 0 to 4% at ñ<sub>1</sub>ò<sub>3</sub>ó<sub>2S</sub>, ñ<sub>1</sub>ò<sub>2</sub>ó<sub>2S</sub>, ñ<sub>2</sub>ò<sub>2</sub>ó<sub>2S</sub>, ñ<sub>2</sub>ò<sub>3</sub>ó<sub>2S</sub>, ñ<sub>3</sub>ò<sub>2</sub>ó<sub>2S</sub>, and ñ<sub>3</sub>ò<sub>3</sub>ó<sub>2S</sub> GABA<sub>A</sub> receptors. Thio-4-PIOL shows greater efficacy at extrasynaptic GABA<sub>A</sub> receptors than at synaptic receptors. It produces effects in animals including hypolocomotion and hyperlocomotion (dependent on dose), anxiogenic effects, pronociceptive effects, impaired spatial learning, and seizures.
Thio-4-PIOL was first described in the scientific literature by 1997. The drug is unlikely to be a candidate for a therapeutic drug due to its undesirable effects, but may be useful in scientific research. It is one of the only GABA<sub>A</sub> receptor agonists to have been comprehensively evaluated in terms of functional activities.