MRK-409, also known as MK-0343, is a GABAA receptor partial agonist.[2]
It was designed to be a non-sedative anxiolytic, however its development was halted because it produced sedation in humans.[3]
Pharmacodynamics
Despite lacking the benzodiazepine chemical structure, MRK-409 acts on the benzodiazepine binding site, it is therefore a nonbenzodiazepine.
MRK-409 binds to the α1, α2, α3 and α5 subunits of the GABAA receptor.[4]
In rats, it produces minimal to no sedation, however it produces sedation in humans at doses above 1 mg.[3][5]
References
- ^ "1,2,4-Triazolo(4,3-b)pyridazine, 7-cyclobutyl-3-(2,6-difluorophenyl)-6-((1-methyl-1H-1,2,4-triazol-5-yl)methoxy)-".
- ^ "MRK-409". go.drugbank.com. Retrieved 2024-02-09.
- ^ a b Atack, John R. (2010). "GABAA receptor alpha2/alpha3 subtype-selective modulators as potential nonsedating anxiolytics". Current Topics in Behavioral Neurosciences. 2: 331–360. doi:10.1007/7854_2009_30. ISBN 978-3-642-02911-0. ISSN 1866-3370. PMID 21309116.
- ^ Atack, J. R.; Wafford, K. A.; Street, L. J.; Dawson, G. R.; Tye, S.; Van Laere, K.; Bormans, G.; Sanabria-Bohórquez, S. M.; De Lepeleire, I.; de Hoon, J. N.; Van Hecken, A.; Burns, H. D.; McKernan, R. M.; Murphy, M. G.; Hargreaves, R. J. (2011). "MRK-409 (MK-0343), a GABAA receptor subtype-selective partial agonist, is a non-sedating anxiolytic in preclinical species but causes sedation in humans". Journal of Psychopharmacology. 25 (3): 314–328. doi:10.1177/0269881109354927. ISSN 1461-7285. PMID 20147571. S2CID 5181868.
- ^ Atack, J. R.; Hallett, D. J.; Tye, S.; Wafford, K. A.; Ryan, C.; Sanabria-Bohórquez, S. M.; Eng, Wai-Si; Gibson, R. E.; Burns, H. D.; Dawson, G. R.; Carling, R. W.; Street, L. J.; Pike, A.; De Lepeleire, I.; Van Laere, K. (2011). "Preclinical and clinical pharmacology of TPA023B, a GABAA receptor α2/α3 subtype-selective partial agonist". Journal of Psychopharmacology. 25 (3): 329–344. doi:10.1177/0269881109354928. ISSN 1461-7285. PMID 20156926. S2CID 37703616.