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- W3213731036 endingPage "108035" @default.
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- W3213731036 abstract "Positive allosteric modulators of γ-aminobutyric acid-A (GABAA) receptors or GABAkines have been widely used medicines for over 70 years for anxiety, epilepsy, sleep, and other disorders. Traditional GABAkines like diazepam have safety and tolerability concerns that include sedation, motor-impairment, respiratory depression, tolerance and dependence. Multiple GABAkines have entered clinical development but the issue of side-effects has not been fully solved. The compounds that are presently being developed and commercialized include several neuroactive steroids (an allopregnanolone formulation (brexanolone), an allopregnanolone prodrug (LYT-300), Sage-324, zuranolone, and ganaxolone), the α2/3-preferring GABAkine, KRM-II-81, and the α2/3/5-preferring GABAkine PF-06372865 (darigabat). The neuroactive steroids are in clinical development for post-partum depression, intractable epilepsy, tremor, status epilepticus, and genetic epilepsy disorders. Darigabat is in development for epilepsy and anxiety. The imidazodiazepine, KRM-II-81 is efficacious in animal models for the treatment of epilepsy and post-traumatic epilepsy, acute and chronic pain, as well as anxiety and depression. The efficacy of KRM-II-81 in models of pharmacoresistant epilepsy, preventing the development of seizure sensitization, and in brain tissue of intractable epileptic patients bodes well for improved therapeutics. Medicinal chemistry efforts are also ongoing to identify novel and improved GABAkines. The data document gaps in our understanding of the molecular pharmacology of GABAkines that drive differential pharmacological profiles, but emphasize advancements in the ability to successfully utilize GABAA receptor potentiation for therapeutic gain in neurology and psychiatry." @default.
- W3213731036 created "2021-11-22" @default.
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- W3213731036 date "2022-06-01" @default.
- W3213731036 modified "2023-10-11" @default.
- W3213731036 title "GABAkines – Advances in the discovery, development, and commercialization of positive allosteric modulators of GABAA receptors" @default.
- W3213731036 cites W1030949942 @default.
- W3213731036 cites W1486365369 @default.
- W3213731036 cites W1499599330 @default.
- W3213731036 cites W1520508152 @default.
- W3213731036 cites W1592645113 @default.
- W3213731036 cites W1593892605 @default.
- W3213731036 cites W1619186117 @default.
- W3213731036 cites W164742581 @default.
- W3213731036 cites W1697749966 @default.
- W3213731036 cites W170920423 @default.
- W3213731036 cites W1837240502 @default.
- W3213731036 cites W1841008104 @default.
- W3213731036 cites W1842711843 @default.
- W3213731036 cites W1894591827 @default.
- W3213731036 cites W1899132045 @default.
- W3213731036 cites W1914929675 @default.
- W3213731036 cites W1948082071 @default.
- W3213731036 cites W1964600153 @default.
- W3213731036 cites W1965666249 @default.
- W3213731036 cites W1967722500 @default.
- W3213731036 cites W1969905874 @default.
- W3213731036 cites W1970448316 @default.
- W3213731036 cites W1972515921 @default.
- W3213731036 cites W1973651679 @default.
- W3213731036 cites W1974286622 @default.
- W3213731036 cites W1975254725 @default.
- W3213731036 cites W1975302642 @default.
- W3213731036 cites W1976440389 @default.
- W3213731036 cites W1977614408 @default.
- W3213731036 cites W1981745669 @default.
- W3213731036 cites W1981850411 @default.
- W3213731036 cites W1981857440 @default.
- W3213731036 cites W1983756509 @default.
- W3213731036 cites W1983923803 @default.
- W3213731036 cites W1984110660 @default.
- W3213731036 cites W1984161481 @default.
- W3213731036 cites W1985639681 @default.
- W3213731036 cites W1987735289 @default.
- W3213731036 cites W1988931452 @default.
- W3213731036 cites W1991542726 @default.
- W3213731036 cites W1991644271 @default.
- W3213731036 cites W2000076844 @default.
- W3213731036 cites W2000314626 @default.
- W3213731036 cites W2000979605 @default.
- W3213731036 cites W2001308171 @default.
- W3213731036 cites W2001619275 @default.
- W3213731036 cites W2005549417 @default.
- W3213731036 cites W2007065735 @default.
- W3213731036 cites W2007911341 @default.
- W3213731036 cites W2009066187 @default.
- W3213731036 cites W2009324406 @default.
- W3213731036 cites W2010504165 @default.
- W3213731036 cites W2011606970 @default.
- W3213731036 cites W2013775967 @default.
- W3213731036 cites W2013917514 @default.
- W3213731036 cites W2015488490 @default.
- W3213731036 cites W2016154588 @default.
- W3213731036 cites W2016321438 @default.
- W3213731036 cites W2016940189 @default.
- W3213731036 cites W2017120126 @default.
- W3213731036 cites W2019879401 @default.
- W3213731036 cites W2019884656 @default.
- W3213731036 cites W2021097774 @default.
- W3213731036 cites W2022279290 @default.
- W3213731036 cites W2024017841 @default.
- W3213731036 cites W2024545561 @default.
- W3213731036 cites W2025256394 @default.
- W3213731036 cites W2025535749 @default.
- W3213731036 cites W2026400701 @default.
- W3213731036 cites W2027622554 @default.
- W3213731036 cites W2028802103 @default.
- W3213731036 cites W2029215893 @default.
- W3213731036 cites W2029771261 @default.
- W3213731036 cites W2032291923 @default.
- W3213731036 cites W2035592411 @default.
- W3213731036 cites W2036335988 @default.
- W3213731036 cites W2038026687 @default.
- W3213731036 cites W2040498823 @default.
- W3213731036 cites W2040700304 @default.
- W3213731036 cites W2040720903 @default.
- W3213731036 cites W2042232934 @default.
- W3213731036 cites W2044558761 @default.
- W3213731036 cites W2045144911 @default.
- W3213731036 cites W2048706813 @default.