Pravadoline, tseem hu ua yeej 48098, (r {{11613) tuaj yeem siv rau hauv cov txheej txheem organic thiab hauv kev tshawb fawb thiab kev tshawb fawb. Molecular Cov Qauv C23h26NN2O3, CAS 92623 -}} {14- {14 {14} {14 {{14} {14,48 g / mol. Nws yog dawb rau greyish dawb crystalline hmoov nrog ib daim foos. Nws muaj qee qhov solubility hauv qee cov kuab tshuaj organic organic, xws li ethanol, dimethyl sulfoxide thiab methyl tert {}} Buth ether. Txawm li cas los xij, nws muaj kev txom nyem solubility hauv cov kuab-polar, xws li n-hephane thiab dihloromethane. Tsis tas li ntawd, cov solubility ntawm cov khoom hauv dej kuj txwv. Qhov cub npau npau yog feem ntau nyob ib ncig ntawm 400 degrees Celsius. Qhov no txhais tau tias nyob rau hauv ib txwm muaj siab, nws tsis yooj yim heev. Nws muaj ntau yam kev siv peev xwm, suav nrog cov tshuaj tsis zoo thiab tiv thaiv, nrog rau kev siv hauv neuroscience.
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Tshuaj Cov Qauv |
C23H26N2O3 |
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Muaj pes tsawg leej |
378 |
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Molecular hnyav |
378 |
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m/z |
378 (100.0%), 379 (24.9%), 380 (2.7%) |
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Kev Ntsuam Xyuas |
C, 72.99; H, 6.92; N, 7.40; O, 12.68 |
Pravadolinetau tsim thawj zaug nyob rau xyoo 1980 ua ib qho tshiab anti - o; {otecatory thiab prostaglandin inthibitores. Nws ua los ntawm inhibiting enzyme cyclooxygarease (cox), uas yog koom nrog hauv kev tsim cov khoom sib txuas. Thaum pib, lub peev xwm tau nyob ntawm nws lub peev xwm ua ib qho tshuaj tiv thaiv kev siv tshuaj, zoo ib yam li tsis yog siv tshuaj tiv thaiv (NSAID) zoo li indomethacin. Txawm li cas los xij, thaum cov kev tshawb fawb preclinical ua ntej pom cov txiaj ntsig muaj zog nyob rau hauv cov khoom siv tsawg dua li cov anti- inflammatory kev txiav txim siab. Cov kev tshawb pom no tau pom zoo tias kev ua ntsuas kev txiav txim ncua dhau ntawm nws lub luag haujlwm ua cox inhibitor.
Ntxiv kev tshawb nrhiav tau qhia tias nws tau rau ib chav kawm tshiab ntawm cannabinooid agonists, tshwj xeeb aminoylindes. Nws tau pom tias cuam tshuam nrog cannabinoid recetors, CB1 thiab CB2, uas yog qhov tseem ceeb hauv kev ntsuas mob thiab cov lus teb tsis muaj zog. This discovery marked a significant shift in the understanding of its therapeutic potential, positioning it as a potential treatment for pain and inflammation-related conditions.
Cov kev tshawb fawb tau muaj ntau yam, nrog kev tshawb fawb tshawb xyuas nws cov khoom sib xyaw ua ke, nws cov chaw muag tshuaj hauv kev sib piv rau lwm yam kev ua piv txwv, thiab nws cov peev xwm ua rau Neproxicity. Txoj kev tshawb nrhiav txoj kev pom zoo muab kev pom zoo rau hauv cov qauv, pab hauv kev nkag siab ntawm nws kev sib cuam tshuam nrog cannabinoid receptors. Cov kev tshawb nrhiav hauv tsev tshuaj tau hais txog nws cov cim npe tshwj xeeb, pom qhov txawv ntawm nws los ntawm lwm cov cyclooxygitase inhibitors. Txawm li cas los xij, kev txhawj xeeb txog Nephoxicity, tshwj xeeb tshaj yog nyob rau hauv cov dev, tau sau tseg, tsim nyog tau txais kev tshawb xyuas ntxiv rau nws cov ntaub ntawv kev nyab xeeb.
Kev mob txi cov nyhuv
Yeej 48098 tau muaj dav tau kawm ua tus pleev xim. Nws ua rau muaj kev cuam tshuam analgesic los ntawm kev ua kom cov endogenous canninoid system nyob rau hauv lub hlwb. Cov txheej txheem endogenous cannetates hauv kev cai ntawm kev mob mob, thiab zam kev mob los ntawm kev sib txuas nrog cov cannabinoid recepror. Nws khi rau cov receptors no, yog li txo qhov kev xav mob. Txawm hais tias nws tseem tsis tau siv tau hauv kev tshawb fawb kev coj ua, nws tau nyiam cov kev tshawb fawb dav dav yog cov tshuaj muaj peev xwm ua tau zoo.
Anti mob inflammatory
Ntxiv rau nws cov nyhuv analgesic, yeej 48098 kuj tseem ceeb ua rau qee cov anti {{o {incammatory teebmeem. Nws tuaj yeem cuam tshuam cov tshuaj tiv thaiv thiab cov kev tso tawm ntawm cov mob kho kom haum, yog li txo cov tshuaj o thiab qhov mob uas mob. Qhov no ua rau nws muaj peev xwm nyob rau hauv kev kho mob ntawm qee cov kab mob tshwm sim, xws li mob caj dab, mob plab zom mov thiab mob plab zom mov. Txawm li cas los xij, cov tshuaj feem ntau, cov anti- Cov nyhuv ntawm nws tseem yuav tsum tau tshawb nrhiav thiab chaw kuaj mob kom paub tseeb.
Neuroprotective cuam tshuam
Hauv kev tshawb fawb neuroscience, yeej 48098 yog dav siv los tshawb txog nws lub luag haujlwm hauv kev neuroprot. Kev tshawb fawb qhia tau tias nws tuaj yeem nce cov ciaj sia ntawm cov hlab ntsha hlwb thiab txhawb nqa kev loj hlob ntawm cov kab mob hlab ntsha, uas raug mob rau cov kab mob ntawm cov leeg ntshav. Txawm li cas los xij, kev tshawb fawb hauv thaj chaw no tseem nyob rau hauv nws cov theem thaum ntxov thiab tshawb fawb yog xav tau nyob rau hauv lub neej tom ntej los xyuas nws cov nyhuv neuroprotrotive.
Lwm qhov siv tau
Ntxiv rau cov hom phiaj saum toj no, yeej 48098 kuj tseem kawm thiab siv rau lwm thaj teb, xws li cov kab mob plawv, kev kho mob cancer thiab kev nyuaj siab. Nws qhia qee qhov kev cuam tshuam ntawm cov hlab plawv, suav nrog cov kev cai ntawm cov ntshav siab thiab vasodilation. Tsis tas li ntawd, nws tseem ua rau pom qee qhov ove anti {{{{{3} Cov qog nqaij hlav thiab muaj peev xwm ua rau muaj kev loj hlob ntawm cov qog nqaij hlav cancer. Tsis tas li ntawd, kev sim ua ntej xav tau hais tias nws yuav muaj qee yam kev cuam tshuam ntawm kev ntxhov siab thiab ntxhov siab hauv thaj chaw no tseem muaj tsawg.
Lub tsev tshuaj ntawm kev ua ntawm pradopril yuav nyob ntawm qhov tshwj xeeb daim foos. Cov hauv qab no tham txog nws cov tshuab kev ua ua ib qho tshuaj antihistamine thiab antiarrhythmic tshuaj, feem.
Mechanism ntawm kev ua ntawm antihistamines
Hauv qee kis, pradorine yog siv los ua ib qho tshuaj antihistamine feem ntau ua rau muaj kev tsis taus pa. Antihistamines tsuas yog thaiv cov kev cuam tshuam ntawm cov tshuaj histamine ntawm lub cev los ntawm kev khi rau histamine. Cov kev kho mob los ntawm cov neeg nyob sib raug zoo koom nrog kev ua xua thiab cov txheej txheem ua xua. Pradoline tuaj yeem daws cov tsos mob ntawm cov tsos mob los ntawm kev txwv tsis pub muaj Vasodation, cov leeg mob ua kom zoo nkauj los ntawm kev daws teeb meem rau histamine.
Nws yuav tsum raug sau tseg tias qhov ua tau zoo ntawm praidoline ua ib qho tshuaj antihistamine sib txawv ntawm cov tib neeg, raws li muaj qhov sib txawv rau cov neeg muaj lub siab nyiam rau cov neeg sib txawv ntawm cov neeg sib txawv. Yog li ntawd, thaum siv Pradorine los kho cov tsos mob tsis haum, kev kho yuav tsum tau ua raws li cov xwm txheej tshwj xeeb ntawm tus neeg mob.
Mechanism ntawm kev ua ntawm cov tshuaj antiarrhythmic
Pradobrob kuj tseem siv tau los ua tshuaj tua kab mob, tshwj xeeb tshaj yog nyob rau hauv daim ntawv ntawm Propafenone cov ntsiav tshuaj hydrochloride. Nws lub twj siv tshuaj me me ua haujlwm siv Antiarrhythmic los ntawm kev txwv Sodium raws li kev txwv ntawm lub ntsej muag Myocardial membrane thiab Purkinje fibrane.
Inhibit myocardial mistraction
Propafenone hydrochloride ntsiav tshuaj tuaj yeem xaiv khi rau cov ncauj lus ntawm myocrium raws li cov kab ntawv qhib ntawm cov channel no thiab txo qis sodium ion. Sodium ions yog ib qho ntawm cov tseem ceeb ntawm tiam thiab kev tshaj tawm ntawm cov peev txheej hauv myocardial tau txo cov txheej txheem myocardial yuav txo qis lub neej thiab kev coj ua ntawm morecardial cells. Cov nyhuv no tuaj yeem qeeb lub plawv dhia thiab tsis muaj zog ua haujlwm hauv Myocardial, yog li pab tswj arrhythmia.
Txuas lub sijhawm ntawm kev ua tau zoo
Ntxiv rau inhibiting sodium ion Inclium ion, Propafenone cov ntsiav tshuaj hydrochloride kuj tseem cuam tshuam nrog tus lej calcium thiab ntau ntxiv rau hauv cardiomyocytes. Calcium ions ua lub luag haujlwm tseem ceeb hauv kev them nyiaj rov qab ntawm cov peev txheej ntawm myocardial. Los ntawm kev cuam tshuam rau kev cuam tshuam rau kev cuam tshuam ntawm calcium ions, Propafenone cov ntsiav tshuaj hydrochloride tuaj yeem ua rau lub peev xwm ua tau zoo, yog li qeeb lub sijhawm ntawm lub siab. Cov nyhuv no tuaj yeem tiv thaiv qhov tshwm sim thiab kev loj hlob ntawm arrhythmia sai.
Nce Repolorization Retolalization
Tsis tas li ntawd, Propafenone Hydrochloride ntsiav tshuaj tuaj yeem txhim kho cov poov tshuaj ion EULTEDX thiab txhawb nqa cov txheej txheem recolarization. Kev rov qab yog ib theem tseem ceeb ntawm kev ua kom muaj peev xwm hauv myocardial cell, koom nrog efflux ntawm poov tshuaj ions. Los ntawm kev ua kom zoo nkauj poov tshuaj ion, Propafenone cov tsos mob hydrochloride thiab txhim kho cov tsos mob benolarization luv luv thiab ua kom cov mob retolorization luv luv ntawm cov neeg mob ventricular hypertrophy.
Lub Chaw Muag Tshuaj Tshwj Xeeb Linaze ntawm Pravadoline
Pharmacologism siv tshuab ntawm ntau - hom phiaj synergy
Cox Inhibition thiab cov kev cai ntawm Prostaglandin synthesis
Pravadoline inhibits PGH ₂ Ntau Lawm los ntawm kev sib tw los ntawm cov chaw ua si hauv qab no xws li thromboxane ib ₂ (txa ₂) thiab prostaglandin e ₂ (Pge). Cov ntaub ntawv sim qhia tau tias:
Mouse microsomal qauv: Pravadoline cov khoom pov thawj txhaj tshuaj {}} ywj pheej ntawm prostaglandin synthesis ntawm ib qho kev xav ntawm 5 μ m.
EX Vivo Vascular sim: 0.45 μ m pravadoline tuaj yeem ua rau lub vas hauv kev ua rau muaj tshwm sim los ntawm neuronal stimulation, qhia tau tias nws unceviates du leeg spasm los ntawm kev txo cov PEGE ₂ qib.
CB receptor ua kom thiab endogenous canninoid system txoj cai
Pravadoline, raws li ib nrab cb ₁ / cb ₂ receptor agonist, cov khoom ua yeeb yam hom - qhov sib txawv ntawm kev siv ib qho kev sib txawv
Cov Qauv Txheej Txheem: CB ₁ Receptor IC ₅₀ =3155}}}}} {=3155}}}}}}}}}}}}}}}}}}}}}}}}}}}}}}} nm.
Cov Qauv Mas: CB ₁ Receptor IC ₅₀=319}}}}}}}}}}}}}}} Cov Tsiaj Tsis Txaus Siab Yuav cuam tshuam kev txhais lus hauv chaw kuaj mob.
Tom qab CB receptor ua kom tiav, g i protein inhibits adenyin cyclate (AC) Ib qho ntxiv, Cb ₁ Receptor ua kom muaj zog tuaj yeem txhawb cov potassium ion EULT EUL, ruaj khov neuronal membrane muaj peev xwm, thiab txo cov epileptic tso tawm.
Hla Lub Hom Phiaj Ua Phem
Lub tshuab ua dual me me ntawm kev ua ntawm pravadoline ua rau cov nyhuv synergistic:
Txhim kho anti {{0 - kub ua rau cov kev tawm tsam nruab nrab ntawm qhov kev mob teeb liab
Neuroprotective nyhuv: CB receptor ua kom tiav cox inhibition nyob rau hauv kev txo cov oxiditive kev puas tsuaj los ntawm kev cuam tshuam loj hauv infarct loj hauv cerebral ischemia qauv.
Pharmacological cuam tshuam ntawm cov tshuab khoom
Kev Tsim Kho Mob Cardiovascular
Pravadoline ua yeeb yam koob tshuaj - Cov ntshav siab poob qis hauv Cb ₁ Receptor ua kom tiav:
Kev sim ua haujlwm pab dawb nkaus: Tom qab ib koob ntawm 20 mg, nruab nrab systolic ntshav siab poob los ntawm 15-6 teev ({{} beats / feeb).
Mechanism: Ua kom tau txais CB ₁ receptors hauv cov leeg sib dhos, thaum uas inhibitions cov leeg, thaum uas cuam tshuam nrog cov nyhuv antihyperhtensive. Cov siab ua haujlwm ntawm pravadoline (ntau dua lossis sib npaug zos rau 25%) thiab nce txoj kev pheej hmoo ntawm kev pheej hmoo ntawm lub ntsej muag In auscardular Tachycardia (TDP). Nws cov tshuab muaj feem cuam tshuam nrog poov tshuaj channel (ikr) inhibition thiab lig sodium tam sim no (ina) txhim kho, hais tias nws yuav tsum zam rau cov neeg mob uas muaj qt lub caij nyoog sib nrug.
Lub tshuab ua pa
Tom qab nqus tau pravadoline (0.1 mg), hawb pob cov neeg mob ib zaug (fev ₁) thawj zaug, nrog rau cov kab mob hawb pob. Cov nyhuv no cuam tshuam txog kev ua kom muaj kev ua kom muaj CB ₁ receptors ua rau bronchial du cov leeg consaction, uas txwv nws daim ntawv thov nyob rau hauv kev ua pa.
Tom qab cov tsiaj ua pa siab ntawm pravadoline (ntau dua lossis sib npaug nrog 1 mg / mg / mg / mg / m octered thiab edematous, thiab mucus secition nce. Qhov kev tshwm sim no yuav cuam tshuam nrog cov histamine tso tawm los ntawm kev tsim tawm hauv zos, thiab cov kev xa tawm hauv zos yuav tsum tau ua tiav rau kev nqus pa kom txo cov kev mob tshwm sim kom txo cov kev mob tshwm sim kom txo cov kev mob tshwm sim kom txo cov kev mob tshwm sim.
Kev tiv thaiv kab mob
Tom qab tswj hwm rau cov neeg ua haujlwm pub dawb, lub pob zeb hauv cov ntshav kom tsawg li 20% rau 72 teev, nrog rau qhov txo qis hauv IL-2 kev zais cia. Qhov kev txhaj tshuaj tiv thaiv kab mob no yuav ua rau muaj kev pheej hmoo kis mob, tshwj xeeb tshaj yog cov neeg txhaj tshuaj tiv thaiv kab mob, thiab yuav tsum tau siv nrog kev ceev faj. Ib tus qauv nas pom tias pravadoline tuaj yeem txo cov tshuaj tiv thaiv mob txhaj tshuaj
Lub paj hlwb
Tom qab cov thawj coj txuas ntxiv txuas ntxiv (3 mg / kg / hnub, 1 lub limtiam, qhov tseeb ntawm qhov kev ncua 30% txo qis hauv dopamine qib ua ntej cortex. Cov nyhuv no yuav cuam tshuam nrog overactivation ntawm CB ₁ receptors ua rau inibibition ntawm dopamine tso tawm. Cov nas tig quam qhia tau tias 50% txo qis hauv lub sijhawm chaw nyob tom qab kev tswj hwm, qhia tau tias tsis muaj kev cuam tshuam cerebellar muaj nuj nqi. Kev tshawb fawb ntxiv tau lees paub tias Pravadoline tuaj yeem ua rau tus txha nqaj qaum nyob rau hauv Purchje hlwb thiab cuam tshuam nrog kev kawm kev kawm thiab lub cim xeeb
Cim npe nrov: Pravadoline Cas 92623-83-1, Cov Chaw Tsim Khoom, Chaw Tsim Tshuaj, Hoobkas, lag luam Wholesale, yuav, nqe, loj, rau muag