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Allopregnanolone

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Allopregnanolone, tseem hu ua Sepranolone thiab Isopregnanolone, yog GABA receptor modulating steroid antagonist thiab 11-betahydroxysteroid dehydrogenase hom 1 (11β-HSD1)…

Hauj lwm yam khoom

Cov yam ntxwv yooj yim

khoom npe Allopregnanolone
CAS Number 516-55-2
molecular Formula C21H34O2
Mis Lub Cev 318.5
Synonyms NSC-97078; U-0949; UC-1010; NSC97078; U0949; UC1010; NSC 97078; U 0949; UC 1010; Isopregnanolone; Allopregnanolon; Sepranolone; 516-55-2; 5alpha-Pregnan-3beta-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).

 

Allopregnanolone Cov Lus Qhia

Allopregnanolone, tseem hu ua Sepranolone thiab Isopregnanolone, yog GABA receptor modulating steroid antagonist thiab 11-betahydroxysteroid dehydrogenase hom 1 (11β-HSD1). Sepranolone yog qhov muaj zog loj ntawm cov leeg hlwb, tsim nyob rau hauv lub cev, uas hloov kho qhov tshwm sim ntawm Allopregnanolone (ALLO). ALLO yog qhov muaj zog neurosteroid cuam tshuam txog kev ntxhov siab- thiab kev tsim kev mob ntsig txog ntu ntawm Tourette mus rau OCD, PTSD, kev twv txiaj twv txiaj, kev quav yeeb quav tshuaj, PMDD, Mob caj dab.

 

Allopregnanolone Kev Txom Nyem ntawm Kev Ua

Molecular kev sib cuam tshuam

Allopregnanolone yog ib qho kev tiv thaiv kabmob tsis txaus ua rau lub cev neurosteroid. Nws yog tsim los ntawm progesterone, thiab yog tus qauv zoo tag nrho ntawm qhov kev txiav txim ntawm of-aminobutyric acid (GABA) ntawm GABAA receptor. Allopregnanolone muaj cov teebmeem zoo ib yam li lwm cov qauv sib txawv sib txhawb ntawm GABA kev ua ntawm GABA receptor xws li benzodiazepines, suav nrog anxiolytic, sedative, thiab anticonvulsant kev ua. Endogenously tsim allopregnanolone ua rau lub luag haujlwm neurophysiological los ntawm kev kho kom zoo ntawm GABAA receptor thiab modulating kev ua ntawm ntau yam allosteric modulators thiab agonists ntawm GABAA receptor.

Allopregnanolone ua haujlwm yog qhov muaj txiaj ntsig zoo allosteric modulator ntawm GABAA receptor. Thaum allopregnanolone, zoo ib yam li lwm cov tshuaj tiv thaiv neurosteroids xws li THDOC, kev hloov kho tau zoo txhua GABAA receptor isoforms, cov isoforms uas muaj δ subunits muaj cov yeeb yam loj tshaj. Allopregnanolone kuj tau pom los ua qhov zoo tshaj plaws alleric modulator ntawm GABAA-or receptor, txawm hais tias qhov cuam tshuam ntawm kev ua no tsis meej. Ntxiv rau nws cov kev ua ntawm GABA receptors, allopregnanolone, zoo li progesterone, yog paub tias muaj kev tsis zoo rau tag nrho cov kev hloov kho ntawm nACh receptors, thiab tseem tshwm sim los ua qhov tsis zoo allosteric modulator ntawm 5-HT3 receptor. Nrog rau lwm txoj kev tiv thaiv neurosteroids, allopregnanolone zoo li muaj tsawg lossis tsis muaj kev cuam tshuam ntawm lwm cov roj ntsha ionand-gated ion channels, suav nrog NMDA, AMPA, kainate, thiab glycine receptors.

 

Antidepressant cuam tshuam

Tus txheej txheem uas neurosteroid GABAA receptor PAMs zoo li brexanolone muaj cov tshuaj tiv thaiv kev ntxhov siab tsis paub. Lwm GABAA receptor PAMs, xws li benzodiazepines, tsis xav txog cov tshuaj tiv thaiv kev ntxhov siab thiab tsis muaj pov thawj kev ua tau zoo, txawm tias cov kws kho mob tau sau ntawv rau Alprazolam rau kev nyuaj siab yav dhau los. Neurosteroid GABAA receptor PAMs paub los cuam tshuam nrog GABAA receptors thiab sub-pejxeem sib txawv dua li benzodiazepines. Raws li ua piv txwv, GABAA receptor-potentiating neurosteroids yuav nyiam rau qhov muaj GABAA receptors, thiab txhim kho ob leeg tonic thiab phasic inhibition mediated los ntawm GABAA receptors. Nws tseem muaj peev xwm tias neurosteroids zoo li allopregnanolone tuaj yeem ua rau lwm lub hom phiaj, suav nrog membrane progesterone receptors, T-hom voltage-gated calcium channel, thiab lwm tus, los daws cov teebmeem antidepressant.

 

Daim Ntawv Thov Allopregnanolone

Allopregnanolone yog lub cev tsim tawm cov tshuaj steroid uas ua haujlwm ntawm lub hlwb. Raws li cov tshuaj, nws tau muag hauv qab lub npe Zulresso thiab siv los kho kev nyuaj siab tom qab yug menyuam. Nws yog siv los ntawm kev txhaj tshuaj rau hauv txoj leeg ntev dua 60-teev hauv kev saib xyuas kev kho mob.

Cov kev mob tshwm sim ntawm Allopregnanolone yuav suav nrog kev ua kom tsaug zog, tsaug zog, qhov ncauj qhuav, kub ib ce, thiab tsis nco qab. Nws yog cov neurosteroid thiab ua raws li qhov zoo allosteric modulator ntawm GABAA receptor, lub hom phiaj loj ntawm lub inhibitory neurotransmitter γ-aminobutyric acid (GABA).

Allopregnanolone tau txais kev pom zoo rau kev siv tshuaj kho mob hauv tebchaws Asmeskas xyoo 2019. Tebchaws Asmeskas Cov Khoom Noj thiab Tshuaj (FDA) tau txiav txim siab tias nws yog thawj qhov kev noj tshuaj. Lub sijhawm tswj hwm ntev, nrog rau tus nqi rau kev kho mob ib zaug, tau ua rau muaj kev txhawj xeeb txog kev nkag mus rau ntau tus pojniam.

 

reference

[1] Lionetto L, De Andrés F, Capi M, Curto M, Sabato D, Simmaco M, Bossù P, Sacchinelli E, Orfei MD, Piras F, Banaj N, Spalletta G. LC-MS / MS tib lub sijhawm soj ntsuam ntawm allopregnanolone, epiallopregnanolone, hormanolone, dehydroepiandrosterone thiab dehydroepiandrosterone 3-sulfate hauv tib neeg cov ntshav. Bioanalysis. 2017 Mar; 9 (6): 527-539. doi: 10.4155 / xyoob-2016-0262. PubMed PMID: 28207286.

[2] Horishita T, Yanagihara N, Ueno S, Sudo Y, Uezono Y, Okura D, Minami T, Kawasaki T, Sata T. Neurosteroids allopregnanolone sulfate thiab sulfanolone sulfate muaj ntau cov txiaj ntsig ntawm qhov α sub ntawm cov neuronal voltage-gated sodium raws Nav1.2, Nav1.6, Nav1.7, thiab Nav1.8 qhia hauv xenopus oocytes. Tshuaj loog. 2014 Sep; 121 (3): 620-31. doi: 10.1097 / ALN.0000000000000296. PubMed PMID: 24809977.

[3] Zorumski CF, Paul SM, Covey DF, Mennerick S (Kaum Ib Hlis 2019). "Neurosteroids raws li cov tshuaj tiv thaiv kev ntxhov siab thiab ntxhov siab tshiab: GABA-A receptors thiab tshaj". Neurobiology ntawm Kev Nyuaj Siab. 11: 100196. doi: 10.1016 / j.ynstr.2019.100196. PMC 6804800. PMID 31649968.

[4] Warner, MD; Peabody, CA; Whiteford, HA; Hollister, LE (Lub Plaub Hlis 1988). “Alprazolam yog cov tshuaj tiv thaiv kab mob”. Phau ntawv Journal soj ntsuam kev puas siab puas ntsws. 49 (4): 148–150. ISSN 0160-6689. PMID 3281931.

[5] Srisurapanont, M .; Boonyanaruthee, V. (1997). Alprazolam thiab tus qauv txheem tshuaj tua kab mob hauv kev kho kev ntxhov siab: tshuaj xyuas meta-tsom tshuaj los ntawm cov nyhuv antidepressant. Chaw rau Kev Soj Xyuas thiab Kev Tshaj Tawm (UK). PMID 9175386.

[6] Reddy DS (2010). Neurosteroids: endogenous lub luag haujlwm hauv tib neeg lub hlwb thiab kho kev muaj peev xwm. Prog. Lub Hlwb Res. Kev nce qib hauv Kev Tshawb Fawb. 186. pp. 113–37. doi: 10.1016 / B978-0-444-53630-3.00008-7. ISBN 9780444536303. PMC 3139029. PMID 21094889.

[7] Bullock AE, Clark AL, Grady SR, Robinson SF, Slobe BS, Cim MJ, li al. (Lub Rau Hli 1997). "Neurosteroids modulate nicotinic receptor muaj nuj nqi hauv nas striatal thiab thalamic synaptosomes". Phau ntawv Journal ntawm Neurochemistry. 68 (6): 2412–23. doi: 10.1046 / j.1471-4159.1997.68062412.x. PMID 9166735.

[8] Slavíková B, Bujons J, Matyáš L, Vidal M, Babot Z, Krištofíková Z, Suñol C, Kasal A. Allopregnanolone thiab មានផ្ទៃពោះ analogues hloov kho hauv lub nplhaib C: kev sib txuas thiab kev ua si. J Med Chem. 2013 Mar 28; 56 (6): 2323-36. doi: 10.1021 / jm3016365. PubMed PMID: 23421641.