4-PIOL
Pharmaceutical compound
From Wikipedia, the free encyclopedia
4-PIOL, also known as 5-(4-piperidyl)isoxazol-3-ol, is a GABAA receptor agonist that was derived from THIP (gaboxadol).[1][2][3][4] It is a non-ring-fused analogue of THIP and is also closely structurally related to the Amanita muscaria alkaloid muscimol and the neurotransmitter γ-aminobutyric acid (GABA).[4][5][6]
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| Drug class | GABAA receptor partial agonist |
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| Formula | C8H12N2O2 |
| Molar mass | 168.196 g·mol−1 |
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The drug acts specifically as a low-affinity and low-efficacy partial agonist of the GABAA receptor.[1][2][3][4][5] Its affinity (IC50) for the GABAA receptor is 6–9 μM, whereas that of muscimol is 6 nM, of THIP is 92–130 nM, and of GABA is 18 nM.[7][8][5] 4-PIOL has a predominantly antagonistic profile, but can also act as a high-efficacy partial agonist in some systems.[9] It does not appear to desensitize GABAA receptors, which is in contrast to higher-efficacy agonists.[9][1] This property of 4-PIOL is thought to be related to its low-efficacy agonism.[9][1]
4-PIOL was developed by Povl Krogsgaard-Larsen and colleagues and was first described in the scientific literature by 1987.[10] Potent GABAA receptor modulators, including other partial agonists as well as antagonists, have been derived via structural modification of 4-PIOL.[4][11][3][5][12][13] One notable derivative of 4-PIOL, the antagonist 4-Naph-Me-4-PIOL, shows restored high affinity and potency at the GABAA receptor (binding IC50 = 49; Ki = 90 nM; functional IC50 = 370 nM).[7][8][2][12][14] It has been said to be markedly more potent than the standard GABAA receptor antagonist gabazine.[2][8]