Brexanolone (516-54-1) phofo - Mofani oa Lihlahisoa tsa Baetsi
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Mokhathala

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Tlhaloso ea Sehlahisoa

Litšobotsi tsa Motheo

Name Product Mokhathala
Nomoro ea CAS 516-54-1
Molecular Formula C21H34O2
Boima ba 'mele 318.501
Li-synonyms Letsoalo

Mokhathala

516-54-1

Allotetrahydroprogesterone

Allopregnan-3alpha-ol-20-e le 'ngoe

Ponahalo Pula e tšoeu
Ho Boloka le ho Sebetsana E omme, e lefifi ebile e le 0 - 4 C ka nako e khuts'oane (matsatsi ho isa ho libeke) kapa -20 C nako e telele (likhoeli ho isa ho lilemo) ..

 

Tlhaloso ea Brexanolone

Brexanolone ke e ikhethileng, e sebelisoang ka methapo, e nang le methapo ea methapo e sebetsanang le khatello ea maikutlo e sebelisoang kalafong ea khatello ea maikutlo kamora ho pepa. Litekong tsa kalafo ea prelicensure, kalafo ea brexanolone e ne e sa amahanngoe le sekhahla se eketsehang sa bophahamo ba serum aminotransferase, mme ha e so ka e hokahanngoa le maemo a ho lemala ha sebete ho hlakileng.

Brexanolone hape ke 3-hydroxy-5alpha-pregnan-20-eo sehlopha sa hydroxy se maemong a 3 se nang le alpha-configuration. Ke metabolite ea hormone ea progesterone ea thobalano mme e sebelisetsoa ho phekola khatello ea maikutlo ka mor'a ho pepa ho basali. E na le karolo ea bohlokoa joaloka metabolite ea motho, ho imeloa kelellong, modulator ea GABA, moriana o thethefatsang pelo le o thetsang.

 

Mokhoa oa Ketso oa Brexanolone

Mokhoa oa ketso ea brexanolone ha o tsejoe ka botlalo. Brexanolone ke mofuta o nang le metsi a mangata a allopregnanolone. Allopregnanolone ke metabolite e kholo ea progesterone. Methati ea allopregnanolone e ntse e phahama le progesterone nakong ea bokhachane le e phahameng ka ho fetisisa ho trimester ea boraro. Allopregnanolone ke steroid e matla, e nang le methapo e matla e fetisang thabo ea methapo ea kutlo ka ho feto-fetoha ha molumo oa allosteric ho synaptic le extrasynaptic gamma-aminobutyric acid (GABA) mofuta oa li-receptor. Mofuta oa extrasynaptic GABA oa mofuta oa A o amohela lipakeng tsa thibelo ea tonic e etsang hore mechini ea allopregnanolone e ikhethang ha e bapisoa le benzodiazepines e sebetsanang le thibelo ea phasic ho GABA mofuta oa li-receptor.

 

Kopo ea Brexanolone

Brexanolone ke sethethefatsi sa pele se kileng sa amoheloa ke US FDA ka kotloloho bakeng sa kalafo ea khatello ea maikutlo ea pelehi (PPD) ho basali ba baholo. Kaha PPD, joalo ka mefuta e meng e fapaneng ea khatello ea maikutlo, e tšoauoa ka maikutlo a ho hlonama, ho hloka thuso kapa ho ba molato, ho holofala kelellong, le / kapa mohopolo oa ho ipolaea, ho nkuoa e le boemo bo sokelang bophelo. Liphuputso li fumane hore PPD kannete e ka ba le litlamorao tse mpe ho tlamo ea bo-mme le masea le kholo ea masea hamorao. Nts'etsopele le phumaneho ea brexanolone bakeng sa kalafo ea PPD ho basali ba baholo kamora moo e fana ka kalafo e ncha le e ts'episang moo ho neng ho le teng tse 'maloa pele ho moo. Haholo-holo ts'ebeliso ea brexanolone ho phekoleng PPD e pota-potiloe ke ts'episo hobane e sebetsa e le tlatsetso ea maiketsetso bakeng sa bofokoli bo ka bang teng ho brexanolone e sa feleng (allopregnanolone) ho basali ba kamora ho pepa ba pepesehelang PPD athe meriana e mengata e atisang ho sebelisoa ea ho thibela khatello ea maikutlo e ka baka liketso tse ka lekanyetsa boteng le tšebetso ea lintho tse kang serotonin, norepinephrine, le / kapa monoamine oxidase empa u se ke oa buella mesebetsi e amanang ka kotloloho le PPD joalo ka ho fetoha hoa tlhaho maemong a li-steroid tse sa feleng tsa neuroactive joalo ka allopregnanolone. Mme qetellong, leha brexanolone e kanna ea ba e ntse e le litekong tsa bongaka ho batlisisa bokhoni ba eona ba ho phekola boemo ba lefu la sethoathoa bo phahameng haholo, ho bonahala eka lithuto tse ling li hlotsoe ho fihlela lintlha tsa mantlha tse bapisang katleho ho khoeseng ha baemeli ba mola oa boraro le tharollo ea monyetla oa boemo bo behang bophelo kotsing ea lefu la sethoathoa le brexanolone vs. placebo ha e eketsoa maemong a tloaelehileng a tlhokomelo.

 

Litla-morao le litemoso tsa Brexanolone

Brexanolone e sebelisoa haholo ke litsela tse ngata mme ka hona ha ho na monyetla oa ho ba le litšebelisano tse kholo tsa lithethefatsi. CYP2C9 ke eona feela enzyme ea cytochrome P450 e bonts'itseng e thibetsoe ke brexanolone lithutong tsa vitro. Phuputso ea tšebelisano-mmoho ea bongaka e ile ea hloleha ho bonts'a liphetoho ho pharmacokinetics ha brexanolone e ne e sebelisoa ke phenytoin, substrate ea CYP2C9. Bokhoni ba tlhekefetso le bona bo bontšitsoe bo le tlase, joalo ka ha ho pakoa ke phapang lipakeng tsa litlaleho tse ikhethileng ha li bapisoa le placebo. Mabapi le tšusumetso ea ho holofala ha sebete le liphio ho pharmacokinetics, ho ne ho se na liphetoho ho mamelleheng ho bakuli ba nang le lefu la sebete le itekanetseng ho isa tekanyong, 'me ha ho na liphetoho tse hlokahalang bakeng sa lefu le matla la liphio. Leha ho le joalo, moemeli oa solubilizing SBECD a ka ipokellela bakuli ba nang le ho holofala ho matla ha renal, ka hona brexanolone ha ea lokela ho fuoa bakuli ba nang le lefu la renal.

 

Reference

[1] Meltzer-Brody S, Colquhoun H, Riesenberg R, et al.: Ho entoa ha Brexanolone ho tepella maikutlong kamora 'karolo ea bobeli: liteko tse peli tsa multicentre, tse foufetseng, tse sa sebetseng, tse laoloang ke placebo, mohato oa 3. Lancet 2018; 392: 1058-1070 Crossref, Seithuti sa Google.

[2] Luke DR, Tomaszewski K, Damle B, le al.: Tlhahlobo ea pharmacology ea mantlha le ea bongaka ea sulfobutylether-beta-cyclodextrin (SBECD). J Pharm Sci 2010; 99: 3291-3301 Crossref, Setsebi sa Google.

[3] Brexanolone Injection, bakeng sa Tšebeliso ea Metsing: Tokomane ea Briefing ea Bafani. Cambridge, Mass, Sage Therapeutics, Komiti ea Keletso ea Psychopharmacologic ea Lithethefatsi le Ts'ireletso ea Lithethefatsi le Kopano ea Ts'ireletso ea Lithethefatsi le Tsamaiso ea Likotsi, Nov 2, 2018. Google Scholar.

[4] Luisi S, Petraglia F, Benedetto C, Nappi RE, Bernardi F, Fadalti M, Reis FM, Luisi M, Genazzani AR. Maemo a Serum allopregnanolone ho basali ba baimana: liphetoho nakong ea bokhachane, nakong ea pelehi, le ho bakuli ba nang le khatello e phahameng ea mali. J Kliniki ea Endocrinol Metab. 2000 Phupu; 85 (7): 2429-33. [E fetotsoe].

[5] Paul SM, Purdy RH. Li-steroid tse sa sebetseng. FASEB J. 1992 Mar; 6 (6): 2311-22. [E fetotsoe].

[6] Farrant M, Nusser Z. Mefuta e fapaneng ea sehlooho se thibelang: ts'ebetso ea phasic le tonic ea li-receptor tsa GABA (A). Nat Rev Neurosci. 2005 Mar; 6 (3): 215-29. [E fetotsoe].

[7] Johannsen BM, Larsen JT, Laursen TM, Bergink V, Meltzer-Brody S, Munk-Olsen T. Lebaka La ho shoa ha Basali ba nang le Mathata a Matla a Postpartum Psychiatric. Ke J Psychiatry. 2016 Jun 01; 173 (6): 635-42. [Sengoloa sa mahala sa PMC] [E fetotsoe].

[8] Noorlander Y, Bergink V, van den Berg MP. Ho utloisisoa le ho bona tšebelisano-'moho ea 'm'a le ngoana ka nako ea ho kena sepetlele le ho lokolloa ka khatello ea maikutlo le kamora' pelehi. Bophelo ba Arch Womens Ment. 2008; 11 (1): 49-56. [E fetotsoe].