Levodopa hmoov CAS 59-92-7

Levodopa hmoov, core tivthaiv ntawm levodopa, molecular mis C9H11NO2, CAS 59-92-7, molecular hnyav 165.19, yog ib tug synthesized amino acid. Dawb los yog greyish dawb crystalline hmoov. Melting point 285.5℃(decomposition). Nws muaj iab saj thiab tsis zoo solubility, tsuas yog me ntsis soluble hauv dej, soluble hauv dej kub, dilute acids thiab alkalis, thiab insoluble hauv ethanol, ether, thiab chloroform. Tsis muaj ntxhiab tsw, tsis muaj ntxhiab, tig dub nyob hauv huab cua. Thaum nws ntub, nws yooj yim rau oxidize hauv huab cua thiab xim yuav tsaus. Yooj yim soluble hauv dilute hydrochloric acid thiab formic acid, soluble hauv dej (66mg / ml), yuav luag insoluble hauv ethanol, benzene, chloroform, thiab ethyl acetate. Nws yog ib qho tseem ceeb tshuaj precursor uas yuav hloov mus rau hauv levodopa los ntawm tib neeg lub cev, uas yog ib tug amino acid nrog pharmacological kev ua.

Levodopa hmoov, raws li cov tshuaj precursor ntawm dopamine, tau dhau los ua cov tshuaj tseem ceeb rau kev kho tus kab mob Parkinson txij thaum nws nrhiav tau nyob rau xyoo 1960. Nws cov tshuaj pharmacological tshwj xeeb thiab kev siv dav hauv kev kho mob ua rau nws tuav txoj haujlwm tseem ceeb hauv thaj chaw xws li neuroscience, geriatrics, ophthalmology, thiab lwm yam.

Cov ntsiab lus tseem ceeb: 'tus qauv kub' kev kho mob rau Parkinson's disease thiab syndrome

 

1. Kev txhim kho cov tsos mob ntawm lub cev muaj zog hauv tus kab mob Parkinson
Tom qab dhau los ntawm cov ntshav- hlwb teeb meem, levodopa hloov mus rau hauv dopamine los ntawm dopa decarboxylase nyob rau hauv lub hlwb, ncaj qha ntxiv cov neurotransmitter deficiency tshwm sim los ntawm degeneration ntawm dopaminergic neurons nyob rau hauv substantia nigra striatum txoj kev. Cov teebmeem tseem ceeb ntawm kev kho mob muaj xws li:

Kev txav qeeb: Cov kev tshawb fawb soj ntsuam tau pom tias levodopa tuaj yeem ua rau cov neeg mob taug kev nrawm ntawm 30% -50%, nce ntiv tes tapping zaus los ntawm 40%, thiab txhim kho lawv lub peev xwm ua haujlwm txhua hnub.
Cov leeg rigidity: Los ntawm kev ua kom cov dopamine D2 receptors thiab txo qis kev ua kom tsis muaj zog hauv cov pob txha pob txha, cov leeg nqaij rov qab los zoo li qub. Hauv kev sim tsiaj, levodopa txo cov kev hloov pauv ntawm Parkinson tus qauv nas los ntawm 70%.

 

2. Kev siv txuas ntxiv ntawm Parkinson's syndrome
Ntxiv nrog rau thawj tus kab mob Parkinson, levodopa kuj tseem siv tau rau cov hauv qab no theem nrab lossis keeb kwm ntawm Parkinson's syndrome:

Vascular Parkinson's Syndrome: Txhim kho gait freezing los ntawm mob stroke, ua ke nrog kev cob qhia kev kho mob, tuaj yeem ua rau tus neeg mob taug kev deb li 50%.
Multi system atrophy (MSA): Rau MSA-P hom (Parkinson's type) cov neeg mob, levodopa tuaj yeem txhim kho cov tsos mob ntawm lub cev ib ntus, tab sis lub sijhawm ua haujlwm tau luv luv (feem ntau<2 years).
Progressive supranuclear palsy (PSP): Nws tsis muaj txiaj ntsig tiv thaiv kab mob ntsug ophthalmoplegia, tab sis tuaj yeem ua rau qee qhov txo qis axial leeg rigidity thiab gait mob.

 

3. Kev tswj xyuas lub sijhawm ntev
Qhov kawg ntawm kev siv tshwm sim: Los ntawm kev hloov mus rau cov tshuaj tswj kev tso tawm (xws li levodopa tswj- cov ntsiav tshuaj tso tawm) lossis ua ke nrog catechol-O-methyltransferase (COMT) inhibitors (xws li entecavine), lub sijhawm "qhib" tuaj yeem txuas ntxiv mus rau 4-6 teev.
Dyskinesia: Cov koob tshuaj tsawg, siab - zaus siv tshuaj ntau zaus lossis ua ke nrog cov tshuaj dopamine receptor agonists (xws li pramipexole) yog siv los txo cov tshuaj hloov pauv.
Kev paub tsis meej: Kev siv tshuaj ntau ntawm levodopa tuaj yeem ua rau muaj kev nkag siab ntau ntxiv thiab yuav tsum tau soj ntsuam cov qhab nia MMSE tsis tu ncua thiab hloov kho ntau npaum li cas.

Daim ntawv thov tshwj xeeb scenario: Hla ciam teb tshawb nrhiav los ntawm hepatic encephalopathy rau cov kab mob ophthalmic

 

1. Neurotransmitter kev tswj nyob rau hauv hepatic encephalopathy
Levodopa txhim kho kev nco qab tsis zoo nyob rau hauv hepatic encephalopathy los ntawm cov txheej txheem hauv qab no:

Kev hloov dopamine: Hauv cov neeg mob uas muaj mob cirrhosis, dopamine qib hauv lub hlwb txo qis los ntawm 50%, tab sis levodopa tuaj yeem rov qab mus rau 70% ntawm cov qib qub.
Kev txhim kho ntawm ammonia kam rau ua: Tsiaj thwmsim tau pom tias levodopa ua rau kom cov tshuaj tiv thaiv ntawm nas rau ammonia lom los ntawm peb zaug, uas tej zaum yuav cuam tshuam rau kev txhim kho ntawm glutamine synthetase kev ua.
Kev ua tau zoo ntawm kev kho mob: Ib qho kev soj ntsuam randomized nrog rau 200 tus neeg mob tau pom tias kev sib xyaw ntawm levodopa thiab lactulose tuaj yeem txo qis tus nqi ntawm cov kab mob hepatic encephalopathy los ntawm 40%.

 

2. Cov kev cai ntawm Neuroplasticity hauv kev kho mob amblyopia
Levodopa hmoovtxhawb nqa qhov pom cortex remodeling los ntawm cov hauv qab no:

Dopamine receptor activation: txhim kho cov lus teb pib ntawm cov neurons nyob rau hauv plaub txheej ntawm lub ntsej muag cortex rau qhov muag stimuli, nce qhov sib txawv rhiab heev los ntawm 20% -30%.
Synaptic plasticity enhancement: Hauv cov menyuam yaus uas muaj anisometropic amblyopia, kev sib xyaw ntawm levodopa thiab occlusion therapy tuaj yeem txhim kho qhov pom kev pom los ntawm 0.2-0.3 LogMAR units, zoo dua li pawg occlusion ib leeg.
Kev kho qhov rai: Qhov kev kho mob zoo tshaj plaws tshwm sim 3 lub hlis ua ntej kev kho mob, thiab nws tau pom zoo tias cov kev kho mob yuav tsum tsis pub tshaj 6 lub hlis kom tsis txhob muaj kev phiv.

 

3. Tshawb nrhiav cov kab mob tsawg
Dopa responsive dystonia (DRD): Rau cov neeg mob uas muaj GTP cyclohydrolase-1 (GCH1) hloov pauv noob, cov tshuaj levodopa qis (100-300mg / d) tuaj yeem txo cov tsos mob thiab tsis tas yuav kho lub neej.
Restless Leg Syndrome (RLS): Ib qho refractory RLS uas tsis muaj zog tiv thaiv cov hlau tsis muaj zog, levodopa tuaj yeem ua rau lub sijhawm pw tsaug zog ntev li 50%, tab sis yuav tsum ceev faj kom tsis txhob muaj kev pheej hmoo ntawm cov tsos mob hnyav dua.
Congenital nqaij tawv: Rau cov neeg mob uas muaj CLCN1 noob hloov, levodopa tuaj yeem txhim kho cov leeg nqaij ib ntus, tab sis lub sijhawm ua haujlwm tsuas yog 2-4 teev.

Peb yog cov chaw tsim khoom ntawm levodopa ntuj.

Tom qab 106 xyoo ntawm kev tshawb fawb thiab kev tsim kho, nws tau dhau los ua qhov yooj yim, ua haujlwm tau zoo, thiab muaj txiaj ntsig zoo, thiab tag nrho cov txheej txheem ntawm cov khoom siv raw kuj tau ua kev lag luam. Nyob rau hauv xyoo tas los no, muaj ob peb txoj kev tshawb fawb txog tshuaj synthesis ntawm levodopa, feem ntau suav nrog cov tooj liab - catalyzed hydroxylation cov tshuaj tiv thaiv thiab cov synthesis ntawm levodopa los ntawm ib tug series ntawm cov lus teb nrog resveratrol thiab hydantoin. Txoj kev sib txuas ntawm tooj liab- catalyzed hydroxylation cov tshuaj tiv thaiv yog qhia hauv daim duab hauv qab no:

Lub ntsiab zoo ntawm cov tshuaj synthesis yog tias lub hom phiaj hluavtaws yog qhov tseeb thiab muaj, cov yield yog loj, purity siab.levodopa hmoov, thiab hom ntawm cov khoom muaj feem xyuam xws li los ntawm - cov khoom muaj tsawg, thiab feem ntau ntawm lawv tuaj yeem kwv yees; Qhov tsis zoo tseem ceeb yog tus nqi siab, cov txheej txheem tsim khoom nyuaj, cov xwm txheej hnyav, thiab kev sib cais nyuaj ntawm cov khoom nruab nrab thiab los ntawm - cov khoom los ntawm cov hom phiaj sib txuas.

Lus Cim: BLOOM TECH (Txij li xyoo 2008), ACHIEVE CHEM-TECH yog peb lub koom haum.

Lwm txoj hauv kev rau kev sib xyaw levodopa: muaj ob lub enzymes feem ntau siv hauv microbial enzyme hloov dua siab tshiab, thiab peb tau tshaj tawm, uas yog tyrosine phenol lyase, hydroxylase, thiab transaminase, uas yog siv tsawg dua hauv levodopa synthesis. Nrog L-Tyrosine ua lub substrate, cov lus qhia vector ntawm LMB B2 lub hom phiaj noob tau tsim thiab hloov mus rau hauv E. coli, thiab thaum kawg, levodopa tau ua ke. Cov txheej txheem no yog complex, thiab cov substrate thiab ascorbic acid tau ntxiv, uas nce tus nqi thiab ua rau nws nyuaj rau tswj. Krishnaveni et al. Siv tyrosine ua ib lub substrate los ua ke cov levodopa los ntawm kev hloov pauv ntawm cov kab mob fungal, ntim enzymatic txaj txoj kev, thiab txhim kho kev kaw enzymatic txaj txoj kev (hluav taws xob tsis siv neeg synthesis method). Ntawm lawv, Mina txoj kev siv hluav taws xob tsis siv neeg sib xyaw ua ke muaj qhov txiaj ntsig siab tshaj plaws ntawm 95.9%.

Cov txheej txheem ntawm synthesizing Levodopa hauv chav kuaj feem ntau yog siv phenylalanine ua cov khoom pib thiab npaj los ntawm cov txheej txheem tshuaj tiv thaiv kab mob. Cov nram qab no yog cov ncauj lus kom ntxaws synthesis cov kauj ruam thiab sib npaug tshuaj sib npaug:

Los ntawm cov kauj ruam saum toj no, Levodopa tuaj yeem ua ke hauv chav kuaj. Nws yuav tsum tau muab sau tseg tias thaum lub sij hawm cov txheej txheem synthesis, nws yog ib qho tsim nyog yuav tsum tau xyuam xim rau kev nyab xeeb, tsis txhob sib cuag nrog cov tshuaj lom thiab teeb meem, thiab muab pov tseg kom zoo.

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