4-AHP, also known as 4-(aminomethyl)-1-hydroxypyrazole, is a synthetic GABA<sub>A</sub> receptor agonist related to the alkaloid and Amanita muscaria constituent muscimol.
The drug is a moderately potent and high-efficacy partial to full agonist of the GABA<sub>A</sub> receptor ( = 69âÂÂ108%). It is less potent as a GABA<sub>A</sub> receptor agonist than ó-aminobutyric acid (GABA), muscimol, or gaboxadol (THIP) (e.g., ~30-fold lower affinity and ~24-fold lower activational potency than muscimol), but shows a similar functional activity profile relative to those of GABA and muscimol. The drug is also a high-efficacy partial agonist of the GABA<sub>A</sub>-àreceptor (~4-fold less potent than muscimol). It does not appear to have been evaluated in animals and its effects are unknown. 4-AHP is a close analogue of muscimol, in which the isoxazole ring has been replaced with a pyrazole ring.
4-AHP was first described in the scientific literature by 2013. It is one of only a few known analogues of muscimol that have been found to act as high-efficacy GABA<sub>A</sub> receptor agonists, along with other related compounds such as dihydromuscimol, thiomuscimol, and gaboxadol. This can be attributed to the very strict structural requirements for GABA<sub>A</sub> receptor binding and activation. A number of derivatives of 4-AHP have been synthesized and studied as GABA<sub>A</sub> receptor ligands.