FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4385751511> ?p ?o ?g. }

• W4385751511 endingPage "1863" @default.
• W4385751511 startingPage "1841" @default.
• W4385751511 abstract "Abstract This article describes the critical role of neurosteroids in postpartum depression (PPD) and outlines the landmark pharmacological journey of brexanolone as a first-in-class neurosteroid antidepressant with significant advantages over traditional antidepressants. PPD is a neuroendocrine disorder that affects about 20% of mothers after childbirth and is characterized by symptoms including persistent sadness, fatigue, dysphoria, as well as disturbances in cognition, emotion, appetite, and sleep. The main pathology behind PPD is the postpartum reduction of neurosteroids, referred to as neurosteroid withdrawal, a concept pioneered by our preclinical studies. We developed neurosteroid replacement therapy (NRT) as a rational approach for treating PPD and other conditions related to neurosteroid deficiency, unveiling the power of neurosteroids as novel anxiolytic-antidepressants. The neurosteroid, brexanolone (BX), is a progesterone-derived allopregnanolone that rapidly relieves anxiety and mood deficits by activating GABA-A receptors, making it a transformational treatment for PPD. In 2019, the FDA approved BX, an intravenous formulation of allopregnanolone, as an NRT to treat PPD. In clinical studies, BX significantly improved PPD symptoms within hours of administration, with tolerable side effects including headache, dizziness, and somnolence. We identified the molecular mechanism of BX in a neuronal PPD-like milieu. The mechanism of BX involves activation of both synaptic and extrasynaptic GABA-A receptors, which promote tonic inhibition and serve as a key target for PPD and related conditions. Neurosteroids offer several advantages over traditional antidepressants, including rapid onset, unique mechanism, and lack of tolerance upon repeated use. Some limitations of BX therapy include lack of aqueous solubility, limited accessibility, hospitalization for treatment, lack of oral product, and serious adverse events at high doses. However, the unmet need for synthetic neurosteroids to address this critical condition supersedes these limitations. Recently, we developed novel hydrophilic neurosteroids with a superior profile and improved drug delivery. Overall, approval of BX is a major milestone in the field of neurotherapeutics, paving the way for the development of novel synthetic neurosteroids to treat depression, epilepsy, and status epilepticus. Graphical abstract" @default.
• W4385751511 created "2023-08-12" @default.
• W4385751511 creator A5002821906 @default.
• W4385751511 creator A5037036576 @default.
• W4385751511 creator A5091498548 @default.
• W4385751511 date "2023-08-11" @default.
• W4385751511 modified "2023-10-17" @default.
• W4385751511 title "Preclinical and clinical pharmacology of brexanolone (allopregnanolone) for postpartum depression: a landmark journey from concept to clinic in neurosteroid replacement therapy" @default.
• W4385751511 cites W15119525 @default.
• W4385751511 cites W1512835764 @default.
• W4385751511 cites W1552482204 @default.
• W4385751511 cites W1647312149 @default.
• W4385751511 cites W1660594009 @default.
• W4385751511 cites W1939084108 @default.
• W4385751511 cites W1965231425 @default.
• W4385751511 cites W1966695200 @default.
• W4385751511 cites W1967253824 @default.
• W4385751511 cites W1980923887 @default.
• W4385751511 cites W1982442226 @default.
• W4385751511 cites W1983034344 @default.
• W4385751511 cites W1984548667 @default.
• W4385751511 cites W1984582983 @default.
• W4385751511 cites W1988405118 @default.
• W4385751511 cites W1993904321 @default.
• W4385751511 cites W1994775090 @default.
• W4385751511 cites W1994924064 @default.
• W4385751511 cites W1997933872 @default.
• W4385751511 cites W2004123621 @default.
• W4385751511 cites W2005332203 @default.
• W4385751511 cites W2008044072 @default.
• W4385751511 cites W2009377502 @default.
• W4385751511 cites W2011430874 @default.
• W4385751511 cites W2012767314 @default.
• W4385751511 cites W2017699870 @default.
• W4385751511 cites W2018769555 @default.
• W4385751511 cites W2019599447 @default.
• W4385751511 cites W2020520992 @default.
• W4385751511 cites W2020886601 @default.
• W4385751511 cites W2028466691 @default.
• W4385751511 cites W2031648971 @default.
• W4385751511 cites W2033837647 @default.
• W4385751511 cites W2034446966 @default.
• W4385751511 cites W2037299897 @default.
• W4385751511 cites W2039274241 @default.
• W4385751511 cites W2042563099 @default.
• W4385751511 cites W2042580472 @default.
• W4385751511 cites W2043414873 @default.
• W4385751511 cites W2046566032 @default.
• W4385751511 cites W2047157308 @default.
• W4385751511 cites W2051056852 @default.
• W4385751511 cites W2055973066 @default.
• W4385751511 cites W2055989445 @default.
• W4385751511 cites W2061012355 @default.
• W4385751511 cites W2061028746 @default.
• W4385751511 cites W2061052720 @default.
• W4385751511 cites W2063724743 @default.
• W4385751511 cites W2064785985 @default.
• W4385751511 cites W2065158531 @default.
• W4385751511 cites W2065523429 @default.
• W4385751511 cites W2068156278 @default.
• W4385751511 cites W2068868303 @default.
• W4385751511 cites W2075458520 @default.
• W4385751511 cites W2078357700 @default.
• W4385751511 cites W2084225878 @default.
• W4385751511 cites W2089056970 @default.
• W4385751511 cites W2089265290 @default.
• W4385751511 cites W2092310080 @default.
• W4385751511 cites W2095492353 @default.
• W4385751511 cites W2097288285 @default.
• W4385751511 cites W2098185331 @default.
• W4385751511 cites W2106279703 @default.
• W4385751511 cites W2111671651 @default.
• W4385751511 cites W2113263320 @default.
• W4385751511 cites W2114669966 @default.
• W4385751511 cites W2118505143 @default.
• W4385751511 cites W2118790060 @default.
• W4385751511 cites W2127146014 @default.
• W4385751511 cites W2127483997 @default.
• W4385751511 cites W2130481569 @default.
• W4385751511 cites W2138349706 @default.
• W4385751511 cites W2145087907 @default.
• W4385751511 cites W2147975541 @default.
• W4385751511 cites W2148251372 @default.
• W4385751511 cites W2148377354 @default.
• W4385751511 cites W2148412570 @default.
• W4385751511 cites W2149264570 @default.
• W4385751511 cites W2160297083 @default.
• W4385751511 cites W2161288077 @default.
• W4385751511 cites W2165699104 @default.
• W4385751511 cites W2171196764 @default.
• W4385751511 cites W2268551619 @default.
• W4385751511 cites W2268771058 @default.
• W4385751511 cites W2270012675 @default.
• W4385751511 cites W2282595164 @default.
• W4385751511 cites W2335809235 @default.
• W4385751511 cites W2345911396 @default.
• W4385751511 cites W2346213574 @default.
• W4385751511 cites W2476772099 @default.

• next