Cov yam ntxwv yooj yim

khoom npe	Brexanolone
CAS Number	516-54-1
molecular Formula	C21H34O2
Mis Lub Cev	318.501
Synonyms	Allopregnanolone Brexanolone 516-54-1 Allotetrahydroprogesterone Allopregnan-3alpha-ol-20-ib
tsos	Dawb hmoov
Cia thiab Ua Haujlwm	Qhuav, tsaus thiab nyob rau hauv 0 - 4 C rau lub sij hawm luv (hnub mus rau lub lis piam) lossis -20 C rau lub sij hawm ntev (hli txog xyoo) ..

 

Brexanolone Cov Lus Qhia

Brexanolone yog ib qho tshwj xeeb, muab kev tswj hwm, neuroactive steroidal antidepressant siv rau hauv kev kho mob ntawm kev kho mob nruab nrab-rau-mob hnyav tom qab yug menyuam tas. Hauv prelicensure cov chaw kuaj mob, kev kho mob brexanolone tsis cuam tshuam nrog kev nce ntxiv ntawm cov ntshav aminotransferase kom nce siab ntxiv, thiab nws tsis tau txuas nrog piv txwv ntawm cov kab mob siab mob siab rau txoj kev mob siab.

Brexanolone tseem yog qhov 3-hydroxy-5alpha-cev xeeb tub-20-ib qho uas hydroxy pawg ntawm txoj hauj lwm 3 muaj alpha-teeb tsa. Nws yog ib qho tshuaj metabolite ntawm kev sib deev hormone progesterone thiab siv rau kev kho mob tom qab yug menyuam tas nyob hauv poj niam. Nws muaj lub luag haujlwm xws li tib neeg tshuaj lom neeg, tiv thaiv tshuaj tiv thaiv kab mob, GABA modulator, tshuaj pleev qhov quav thiab ua kom loog.

 

Brexanolone Kev Ntsuas Ntawm Kev Ua

Cov tshuab ntawm kev ua ntawm brexanolone tsis paub tag nrho. Brexanolone yog qhov tsim aqueous ntawm allopregnanolone. Allopregnanolone yog qhov tseem ceeb ntawm kev paub txog progesterone. Qib ntawm allopregnanolone txuas ntxiv nce nrog progesterone thaum cev xeeb tub nrog qhov siab tshaj plaws hauv peb lub hlis thib peb. Allopregnanolone yog ib qho muaj zog, endogenous neuroactive steroid uas hloov kho qhov tsis txaus siab neuronal los ntawm kev hloov kho zoo tag nrho ntawm qhov kev ua kom zoo rau kev tiv thaiv synaptic thiab extrasynaptic gamma-aminobutyric acid (GABA) hom A receptors. Extrasynaptic GABA hom A receptors mediate tonic inhibition uas ua rau allopregnanolone cov txheej txheem tshwj xeeb thaum piv nrog benzodiazepines uas sib cais phasic inhibition ntawm GABA hom A receptors.

 

Daim Ntawv Thov Brexanolone

Brexanolone yog thawj cov tshuaj uas tau pom zoo los ntawm Asmeskas FDA tshwj xeeb rau kev kho mob tom qab yug menyuam (PPD) hauv cov pojniam laus. Txij li PPD, zoo li ntau lwm yam kev nyuaj siab, tus yam ntxwv muaj kev tu siab, tsis muaj nqis lossis txhaum, qhov tsis pom kev, thiab / lossis tej zaum kev xav tua tus kheej, nws raug suav hais tias yog kev mob kev phom sij. Cov kev tshawb fawb pom tau hais tias PPD tuaj yeem ua rau muaj kev cuam tshuam zoo rau leej niam-menyuam daim ntawv cog lus thiab tom qab kev loj hlob ntawm cov menyuam mos. Kev tsim kho thiab muaj khoom siv ntawm brexanolone rau kev kho mob ntawm PPD hauv cov poj niam laus tom qab tau muab txoj kev kho tshiab thiab muaj txiaj ntsig qhov twg muaj ob peb nyob ua ntej. Tshwj xeeb, kev siv cov brexanolone hauv kev kho PPD yog ib puag ncig nrog kev cog lus vim nws ua ib feem raws li cov khoom siv hluavtaws ntxiv rau qhov muaj peev xwm ua tsis zoo ntawm cov kab mob endogenous brexanolone (allopregnanolone) hauv postpartum cov poj niam ua rau tiv thaiv PPD tab sis feem ntau siv los tiv thaiv cov tshuaj tiv thaiv kev nyuaj siab uas ua rau muaj feem cuam tshuam uas hloov kho qhov muaj thiab kev ua haujlwm ntawm cov tshuaj zoo li serotonin, norepinephrine, thiab / lossis monoamine oxidase tab sis tsis txhob sib kho cov dej num ncaj qha nrog PPD zoo li cov kev hloov pauv hauv cov theem ntawm cov tshuaj tiv thaiv neuroactive steroids zoo li allopregnanolone. Thiab thaum kawg, txawm hais tias brexanolone kuj tseem tab tom soj ntsuam sim los tshawb nrhiav nws lub peev xwm kho super-refractory xwm txheej mob epilepticus, nws pom tias qee qhov kev tshawb fawb tau ua tsis tau raws li cov thawj cov ntsiab lus uas piv rau kev ua tiav ntawm kev txiav ntawm cov kab mob thib peb thiab kev daws teeb meem uas muaj peev xwm Lub neej muaj kev phom sij tuaj yeem muaj kev pheej hmoo nrog epicpticus nrog brexanolone thiab cov placebo thaum ntxiv rau hauv kev kho mob.

 

Brexanolone Sab Sijhawm & Ceeb Toom

Brexanolone tau dav dav los ntawm ntau txoj hauv kev thiab yog li tsis zoo li muaj kev cuam tshuam loj heev txog tshuaj-yeeb tshuaj. CYP2C9 yog qhov tsuas yog cytochrome P450 enzyme uas tau pom tias yog inhibited los ntawm brexanolone hauv kev tshawb fawb hauv vitro. Kev soj ntsuam kev sib cuam tshuam ua tsis tau los qhia txog txhua yam kev hloov pauv hauv pharmacokinetics thaum brexanolone tau nrog ua ke nrog phenytoin, CYP2C9 substrate. Kev tsim txom lub peev xwm tau pom tau tias nws tsis tshua muaj siab, raws li pom los ntawm qhov tsis muaj qhov sib txawv hauv cov ntawv tshaj qhia piv nrog cov placebo. Hais txog kev cuam tshuam ntawm hepatic thiab lub raum tsis zoo ntawm cov tshuaj pharmacokinetics, tsis muaj kev hloov pauv hauv kev mob siab rau hauv cov neeg mob uas muaj mob hnyav mus rau mob siab thiab mob hnyav, thiab tsis muaj kev kho kom haum rau lub raum mob hnyav. Txawm li cas los xij, solubilizing tus neeg sawv cev SBECD tuaj yeem ntau hauv cov neeg mob uas lub raum ua tsis zoo, thiab yog li brexanolone yuav tsum tsis txhob muab rau cov neeg mob uas mob raum kawg.

 

reference

[1] Meltzer-Brody S, Colquhoun H, Riesenberg R, li al :: Kev txhaj tshuaj rau Brexanolone hauv kev nyuaj siab tom qab: ob lub ntsej muag multicentre, ob-dig muag, randomized, tshuaj placebo, theem 3 sim. Ncig Teb Chaw 2018; 392: 1058–1070 Crossref, Google Scholar.

[2] Lukas DR, Tomaszewski K, Damle B, li al .: Tshuaj xyuas qhov yooj yim thiab chaw muag tshuaj ntawm sulfobutylether-beta-cyclodextrin (SBECD). J Pharm Sci 2010; 99: 3291–3301 Crossref, Google Neeg Kawm.

[3] Txoj Kev Txhaj Tshuaj Brexanolone, rau Kev Siv Intravenous: Daim Ntawv Sau Qhia Me Me. Cambridge, Mass, Sage Therapeutics, Psychopharmacologic Pawg Neeg Qhuab Qhia Hauv Tshuaj thiab Tshuaj thiab Kev Nyab Xeeb thiab Kev Nyab Xeeb Tshuaj thiab Lub Rooj Sib Tham, Lub Kaum Hli 2, 2018. Google Scholar.

[4] Luisi S, Petraglia F, Benedetto C, Nappi RE, Bernardi F, Fadalti M, Reis FM, Luisi M, Genazzani AR. Ntshav theem allopregnanolone hauv cov poj niam cev xeeb tub: hloov pauv thaum cev xeeb tub, thaum yug menyuam, thiab hauv cov neeg mob ntshav siab. J Clin Endocrinol Metab. 2000 Jul; 85 (7): 2429-33. [PubMed].

[5] Paul SM, Purdy RH. Neuroactive steroids. FASEB J. 1992 Mar; 6 (6): 2311-22. [PubMed].

[6] Farrant M, Nusser Z. Kev hloov pauv ntawm lub ntsiab lus: kev ua kom phasic thiab tonic ua haujlwm ntawm GABA (A) receptors. Nat Rev Neurosci. 2005 Mar; 6 (3): 215-29. [PubMed].

[7] Johannsen BM, Larsen JT, Laursen TM, Bergink V, Meltzer-Brody S, Munk-Olsen T. Txhua Tus Ua Rau Pej Xeem hauv Cov Poj Niam Muaj Teeb Meem Tom Qab Pauv Kev Puas Siab puas ntsws. Am J Lub Siab Ntsws. 2016 Jun 01; 173 (6): 635-42. [PMC cov lus pub dawb] [PubMed].

[8] Noorlander Y, Bergink V, van den Berg MP. Nkag siab thiab pom txoj kev sib tham ntawm leej niam-menyuam thaum sijhawm pw hauv tsev kho mob thiab tso tawm tom qab yug menyuam thiab lub siab ntsws. Arch Womens Qhia Txog Kev Noj Qab Haus Huv. Xyoo 2008; 11 (1): 49-56. [PubMed].

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