tpa-023 tpa-023 tpa-023 (mk-0777) is an anxiolytic drug with a novel chemical structure, which is used in scientific research. it has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic. it is a subtype-selective, mixed allosteric modular at the benzodiazepine location on gabaa receptors, where it acts as a partial agonist at the α2 and α3 subtypes, but as a silent antagonist at α1 and α5 subtypes. it has primarily anxiolytic and anticonvulsant effects in animal tests, but with no sedative effects even at 50 times the effective anxiolytic dose. tpa-023clinical dataother namesmk-0777routes ofadministrationby mouthpharmacokinetic datametabolismliverelimination half-life6.7 hoursidentifiers iupac name 7-(1,1-dimethylethyl)-6-(2-ethyl-2h-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolopyridazine cas number252977-51-8 ypubchem cid9908684chemspider8084336unii1fi3ktc550comptox dashboard (epa)dtxsid10179938 chemical and physical dataformulac20h22fn7omolar mass395.442 g·mol−13d model (jsmol)interactive image smiles cc(c)(c)c2=cc3nnc(-c1ccccc1f)n3n=c2occ4ncnn4cc inchi inchi=1s/c20h22fn7o/c1-5-27-17(22-12-23-27)11-29-19-14(20(2,3)4)10-16-24-25-18(28(16)26-19)13-8-6-7-9-15(13)21/h6-10,12h,5,11h2,1-4h3key:qkiwqblntsqoly-uhfffaoysa-n (verify) in human trials on healthy volunteers, tpa-023 was comparable to lorazepam, but had much less side effects on cognition, memory, alertness or coordination. in phase ii trials, the compound was significantly superior to placebo without inducing sedation. the clinical development was halted due to preclinical toxicity (cataract) in long term dosing studies. tpa-023 is well absorbed following oral administration and extensively metabolised by the liver, with a half-life of 6.7 hours. the main enzyme involved in its metabolism is cyp3a4, with some contribution by cyp3a5.