TPA-023
Chemical compound
From Wikipedia, the free encyclopedia
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 mixed, subtype-selective ligand of the benzodiazepine site of α1, α2, α3, and α5-containing GABAA receptors, where it acts as a partial agonist at benzodiazepine sites of the α2 and α3-containing subtypes, but as a silent antagonist at α1 and α5-containing subtypes.[1] It has primarily anxiolytic and anticonvulsant effects in animal tests, but with no sedative effects even at 50 times the effective anxiolytic dose.[2][3]
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| Other names | MK-0777 |
| Routes of administration | By mouth |
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| Metabolism | liver |
| Elimination half-life | 6.7 hours |
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| Chemical and physical data | |
| Formula | C20H22FN7O |
| Molar mass | 395.442 g·mol−1 |
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In human trials on healthy volunteers, TPA-023 was comparable to lorazepam, but lacked negative effects on cognition, memory, alertness or coordination seen with the latter drug.[4] 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.[5][6] TPA-023 is well absorbed following oral administration and extensively metabolised by the liver, with a half-life of 6.7 hours.[7] The main enzyme involved in its metabolism is CYP3A4, with some contribution by CYP3A5.[8]