Brexanolone (516-54-1) powder - Wopanga Mafakitala Opanga
AASraw imapanga ufa wa Cannabidiol (CBD) ndi Hemp Mafuta Ofunika ambiri!

Zowonjezera

mlingo: Category:

Mafotokozedwe Akatundu

Makhalidwe Abwino

Name mankhwala Zowonjezera
Nambala ya CAS 516-54-1
Molecular Formula C21H34O2
Kulemera kwa Fomu 318.501
Mafananidwe Kuthamanga

Zowonjezera

516-54-1

Malangizo: Allotetrahydroprogesterone

Allopregnan-3alpha-ol-20-mmodzi

Maonekedwe White powder
Kusungirako ndi Kusamalira Wouma, wamdima ndi 0 - 4 C kwakanthawi kochepa (masiku mpaka masabata) kapena -20 C kwakanthawi (miyezi mpaka zaka) ..

 

Kufotokozera kwa Brexanolone

Brexanolone ndi yapadera, yoperekedwa kudzera m'mitsempha, neuroactive steroidal antidepressant yomwe imagwiritsidwa ntchito pochiza kupsinjika kwapakatikati mpaka kubereka. Poyeserera koyambirira kwamankhwala, mankhwala a brexanolone sanalumikizidwe ndi kuchuluka kwa seramu aminotransferase, ndipo sikunalumikizidwe ndi zochitika zovulala zowopsa za chiwindi.

Brexanolone imakhalanso 3-hydroxy-5alpha-pregnan-20-m'modzi momwe gulu la hydroxy lomwe lili pamalo 3 limasinthira alpha. Ndi metabolite wa mahomoni ogonana a progesterone omwe amagwiritsidwa ntchito pochiza kukhumudwa kwa amayi atabereka. Imagwira ngati metabolite ya munthu, antidepressant, modulator ya GABA, mankhwala oletsa kumva kupweteka komanso okhazika mtima pansi.

 

Njira Yogwirira Ntchito ya Brexanolone

Njira yogwiritsira ntchito brexanolone sichidziwika bwino. Brexanolone ndimapangidwe amadzimadzi a allopregnanolone. Allopregnanolone ndi metabolite yayikulu ya progesterone. Maseŵera a allopregnanolone akupitirizabe kukwera ndi progesterone panthawi yoyembekezera ndi apamwamba kwambiri m'zaka zitatu zachitatu. Allopregnanolone ndi yamphamvu, yopatsa mphamvu ya neuroactive steroid yomwe imathandizira kusunthika kwa mitsempha kudzera mwa kusinthasintha kwama allosteric pa synaptic ndi extrasynaptic gamma-aminobutyric acid (GABA) mtundu wa receptors. The extrasynaptic GABA mtundu A receptors amathandizira kupondereza kwa tonic komwe kumapangitsa makina a allopregnanolone kukhala osiyana poyerekeza ndi benzodiazepines omwe amalumikizana ndi zoletsa za phasic ku GABA mtundu A receptors.

 

Kugwiritsa ntchito Brexanolone

Brexanolone ndiye mankhwala oyamba kuvomerezedwa ndi US FDA makamaka pochiza kupsinjika kwa pambuyo pobereka (PPD) mwa akazi achikulire. Popeza PPD, monga mitundu ina ya kukhumudwa, imadziwika ndikumva chisoni, kudziona ngati wopanda pake kapena kudziimba mlandu, kuwonongeka kwamalingaliro, komanso / kapena malingaliro ofuna kudzipha, zimawerengedwa kuti ndiwowopsa. Kafukufuku apeza kuti PPD imatha kukhala ndi zotsatirapo zoyipa kwambiri pa mgwirizano wamayi ndi khanda komanso kukula kwa khanda pambuyo pake. Kukula ndi kupezeka kwa brexanolone yothandizira PPD mwa akazi achikulire pambuyo pake kumapereka chithandizo chatsopano komanso chodalirika pomwe panali ochepa kale. Makamaka, kugwiritsidwa ntchito kwa brexanolone pochiza PPD kwazunguliridwa ndi lonjezo chifukwa limakhala ngati chowonjezera chothandizira kuperewera kwa ma brexanolone (allopregnanolone) azimayi omwe abereka pambuyo pobereka omwe atengeke ndi PPD pomwe mankhwala ambiri omwe amagwiritsidwa ntchito pothana ndi zipsinjo amatha kuchititsa zomwe zingachitike sinthani kupezeka ndi zochitika za zinthu monga serotonin, norepinephrine, ndi / kapena monoamine oxidase koma osayimira zochitika zomwe zikugwirizana ndi PPD monga kusinthasintha kwachilengedwe m'magulu amitsempha am'mitsempha amitsempha monga allopregnanolone. Ndipo pamapeto pake, ngakhale brexanolone ikhozanso kukumana ndi mayesero azachipatala kuti ifufuze za kuthekera kwake kothana ndi vuto la epilepticus, zikuwoneka kuti maphunziro enawa alephera kukwaniritsa mathero oyambira omwe amafanizira kupambana pakuletsa kwa omwe akuchita mzere wachitatu ndikuwongolera zomwe zingachitike chiopsezo cha moyo khunyu ndi brexanolone vs.

 

Zotsatira za Brexanolone & Chenjezo

Brexanolone imagwiritsidwa ntchito kwambiri ndi njira zambiri ndipo motero sizimakhala ndi mwayi wogwiritsa ntchito mankhwala osokoneza bongo. CYP2C9 ndiye enzyme yokhayo ya cytochrome P450 yomwe yawonetsa kuti yaletsedwa ndi brexanolone mu maphunziro a vitro. Kafukufuku wazachipatala adalephera kuwonetsa kusintha kulikonse mu pharmacokinetics pomwe brexanolone idayang'aniridwa ndi phenytoin, gawo la CYP2C9. Kuthekera kwa nkhanza kwawonetsedwanso kuti ndi kotsika, monga zikuwonekeranso chifukwa chosasiyana pamalipoti okhudzidwa poyerekeza ndi placebo. Pazokhudzana ndi kuwonongeka kwa chiwindi ndi impso pa pharmacokinetics, sipanakhale kusintha pakulekerera kwa odwala omwe ali ndi matenda owopsa a chiwindi, ndipo palibe kusintha kwamankhwala komwe kumafunikira pamatenda owopsa a impso. Komabe, SBECD yothandizira kusungunuka imatha kudziunjikira mwa odwala omwe ali ndi vuto lalikulu la impso, motero brexanolone sayenera kuperekedwa kwa odwala omwe ali ndi vuto la impso.

 

Reference

[1] Meltzer-Brody S, Colquhoun H, Riesenberg R, ndi al: Brexanolone jakisoni pakumva kupsinjika kwa post-partum: ma multicentre awiri, akhungu awiri, osasinthika, olamulidwa ndi placebo, mayeso a 3. Lancet 2018; 392: 1058-1070 Crossref, Google Scholar.

[2] Luke DR, Tomaszewski K, Damle B, et al. Kuwunikira mankhwala oyambira komanso azachipatala a sulfobutylether-beta-cyclodextrin (SBECD). J Pharm Sci 2010; 99: 3291-3301 Crossref, Google Scholar.

[3] Brexanolone jekeseni, Wogwiritsa Ntchito Mitsempha: Sponsor Briefing Document. Cambridge, Mass, Sage Therapeutics, Psychopharmacologic Committee Advisory Committee ndi Chitetezo cha Mankhwala Osokoneza bongo ndi Msonkhano Wachitetezo cha Mankhwala Osokoneza Ngozi, Nov 2, 2018. Google Scholar.

[4] Luisi S, Petraglia F, Benedetto C, Nappi RE, Bernardi F, Fadalti M, Reis FM, Luisi M, Genazzani AR. Maselo a serum allopregnanolone mwa amayi apakati: kusintha pakakhala ndi pakati, pakubereka, komanso kwa odwala omwe ali ndi matenda oopsa. J Clin Endocrinol Metab. 2000 Jul; 85 (7): 2429-33. [Adasankhidwa].

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

[6] Farrant M, Nusser Z. Kusiyanasiyana pamutu woletsa: phasic and tonic activation ya GABA (A) receptors. Nat Rev Neurosci. 2005 Mar; 6 (3): 215-29. [Adasankhidwa].

[7] Johannsen BM, Larsen JT, Laursen TM, Bergink V, Meltzer-Brody S, Munk-Olsen T. Zomwe Zimayambitsa Kufa Kwa Amayi Omwe Ali Ndi Matenda Oopsa a Postpartum Psychiatric. Ndine J Psychiatry. 2016 Jun 01; 173 (6): 635-42. [Nkhani yaulere ya PMC] [Adasankhidwa].

[8] Noorlander Y, Bergink V, van den Berg MP. Kuzindikira ndikuwona kulumikizana kwa mayi ndi mwana nthawi yachipatala ndikumasulidwa mu kukhumudwa pambuyo pobereka ndi matenda amisala. Arch Womens Ment Health. 2008; 11 (1): 49-56. [Adasankhidwa].