Primidone(link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/primidone-powder-cas-125-33-7.html) yog ib qho tshuaj tiv thaiv kab mob uas yog cov tshuaj isoprene nrog cov qauv molecular ntawm C12H14N2O2 thiab qhov hnyav molecular ntawm 218.26. Nws yog dawb los yog lub teeb daj siv lead ua hmoov, tsis muaj ntxhiab thiab tsis qab. Yuav luag insoluble hauv dej, tab sis yooj yim soluble nyob rau hauv chloroform, benzene, ethanol, acetone thiab lwm yam organic solvents. Nyob rau hauv alkaline los yog acidic tej yam kev mob, nws yog yooj yim hydrolyzed. Tus txheeb ze ruaj khov, tsis yooj yim cuam tshuam hauv huab cua qhuav. Nyob rau hauv qhov kev txiav txim ntawm muaj zog acid, muaj zog alkali, oxidant, ozone, ultraviolet hluav taws xob, thiab lwm yam, nws yog ib qho yooj yim rau decompose thiab degrade. Nws muaj qee yam toxicity thiab tuaj yeem ua rau lom thiab tuag taus. Kev ntsuas kev nyab xeeb thiab kev tiv thaiv ntsig txog yuav tsum tau ua raws li kev npaj, khaws cia thiab siv.
Cov khoom siv tshuaj ntawm Primidone.
1. Acidity thiab Alkalinity
Primidone yog ib qho tseem ceeb tsis muaj zog nrog pKa tus nqi ntawm 7.0-7.5. Nyob rau hauv acidic tej yam kev mob, Primidone yog yooj yim hydrolyzed los tsim lub ntsiab metabolites phenobarbital thiab phenylethylmalonamide (PEMA). Raws li alkaline tej yam kev mob, Primidone yog nquag mus rau sodium lauryl sulfate-ethanol extraction kom tau nws dawb alkaline xeev. Tsis tas li ntawd, Primidone tuaj yeem muaj cov tshuaj acid-puag nrog qee cov tshuaj lossis cov khoom xyaw, cuam tshuam rau lawv qhov nqus thiab cov metabolism.
2. Redox
Primidone nws tus kheej tsis nquag rau redox cov tshuaj tiv thaiv. Txawm li cas los xij, nyob rau hauv kev ua ntawm qee cov oxidants, xws li hydrogen peroxide, hydrogen peroxide, chromic acid, thiab lwm yam, Primidone yog nquag oxidation cov tshuaj tiv thaiv thiab tsim cov khoom oxidation sib xws. Tsis tas li ntawd, nyob rau hauv kev txo qis, Primidone yog nquag hydrolysis thiab generates phenobarbital thiab PEMA.
3. Cov tshuaj tiv thaiv esterification
Primidone muaj ob pawg carboxyl functional thiab ib pawg C-O-C txuas ester, yog li nws yog nquag esterification. Primidone tuaj yeem hnov mob nrog qee cov cawv cawv los tsim cov Primidone esters sib xws, thiab cov khoom esterified no yuav muaj cov tshuaj tiv thaiv kab mob.
4. Cov tshuaj tiv thaiv electrophilic ntxiv
Primidone muaj ib daim ntawv cog lus unsaturated, yog li cov tshuaj electrophilic ntxiv tuaj yeem tshwm sim. Raws li qhov kev txiav txim ntawm qee cov tshuaj electrophilic reagents, xws li halogen, nitro, carboxyl, thiab lwm yam, Primidone yog cov tshuaj tiv thaiv ntxiv los tsim cov khoom sib txuas ntxiv.
5. Amination cov tshuaj tiv thaiv
Primidone muaj cov amino functional pab pawg, yog li nws yog nquag mus rau amination cov tshuaj tiv thaiv. Raws li qhov kev txiav txim ntawm qee cov amino reagents, xws li dej ammonia, ethylenediamine, thiab lwm yam, Primidone yog nquag rau amination cov tshuaj tiv thaiv thiab tsim cov khoom sib xws.
6. Cov tshuaj tiv thaiv photochemical
Primidone yooj yim cuam tshuam los ntawm ultraviolet hluav taws xob. Hauv cov tshuaj tiv thaiv photochemical, Primidone yog qhov ua rau tawg lossis lub log ntxiv cov tshuaj tiv thaiv los tsim cov khoom lag luam photochemical.
Nyob rau hauv luv luv, Primidone yog ib tug compound nrog ntau yam tshuaj xws li acidity thiab alkalinity, redox khoom, esterification cov tshuaj tiv thaiv, electrophilic ntxiv cov tshuaj tiv thaiv, amination cov tshuaj tiv thaiv, thiab photochemical tshuaj tiv thaiv. Kev saib xyuas tshwj xeeb yuav tsum tau them rau kev nyab xeeb thiab kev tiv thaiv kev ntsuas thaum npaj, khaws cia thiab siv.
Cov qauv molecular ntawm Primidone muaj tsib lub nplhaib heterocyclic (2,4-diazacyclohexanone nplhaib), ob pawg methyl thiab ib pawg ethoxy. Lub "C" hauv nws cov qauv molecular sawv cev rau cov pa roj carbon, uas ua raws li kev sib txuas hauv Primidone cov qauv molecular, thaum "H" sawv cev rau hydrogen atom, uas tswj cov molecular kev ncaj ncees. Tsis tas li ntawd, "N" sawv cev rau nitrogen atom, "O" sawv cev rau oxygen atom, thiab "E" sawv cev rau pawg ethoxy.
Cov qauv molecular ntawm Primidone tuaj yeem piav qhia los ntawm ntau txoj hauv kev, feem ntau yog siv cov kab kos duab kab thiab molecular orbital. Nyob rau hauv ib tug linear qauv, txhua atom ntawm cov tshuaj molecular mis yog kev cob cog rua rau tsim ib tug molecular saw raws li kev sib raug zoo ntawm cov atoms nyob rau hauv lub molecule. Daim duab molecular orbital qhia txog kev sib cuam tshuam ntawm cov pa roj carbon thiab nitrogen atoms thiab kev faib cov huab cua hluav taws xob, yog li nthuav tawm cov khoom siv tshuaj thiab cov tshuaj tiv thaiv hauv Primidone molecule.
Primidone yog ib qho tshuaj siv dav siv los kho mob qaug dab peg thiab tshee. Nkag siab txog cov khoom siv tshuaj pharmacokinetic ntawm Primidone yog qhov tseem ceeb rau kev ua kom zoo rau nws siv thiab saib xyuas nws txoj kev nyab xeeb. Pharmacokinetic zog ntawm cov tshuaj muaj xws li nqus, faib, metabolism, thiab excretion. Hauv qab no yog cov lus qhia ntxaws:
1. Kev nqus dej:
Primidone yog ib qho tshuaj ntawm qhov ncauj uas nqus los ntawm txoj hnyuv. Tus nqi thiab qhov nqus ntawm nws qhov sib txawv ntawm tus kheej mus rau ib tus neeg. Nyob rau hauv ib txwm muaj xwm txheej, Primidone yog absorbed tag nrho nyob rau hauv lub plab hnyuv ib ntsuj av, tab sis qhov ceev thiab npaum li cas ntawm nws nqus tau txo tom qab noj mov. Yog li, cov neeg mob raug qhia kom noj Primidone 2 teev ua ntej lossis tom qab noj mov.
Ntxiv nrog rau kev tswj hwm qhov ncauj, Primidone kuj tuaj yeem muab intramuscularly lossis intravenously, tab sis qhov no tsis tshua siv.
2. Kev faib tawm:
Primidone yog dav faib nyob rau hauv lub cev, feem ntau nyob rau hauv daim siab, nqaij, raum thiab hlwb ntaub so ntswg. Nws tseem tuaj yeem hla cov ntshav-hlwb teeb meem, nkag mus rau hauv nruab nrab lub paj hlwb, thiab ncav cuag cov ntsiab lus zoo sib xws hauv cov ntaub so ntswg hauv hlwb xws li cov ntshav. Nws cov yam ntxwv kev faib tawm feem ntau yog txiav txim siab los ntawm cov qauv molecular thiab cov khoom siv lub cev ntawm cov tshuaj.
3. Metabolism:
Primidone yog metabolized nyob rau hauv lub cev rau hauv Phenobarbital thiab lwm yam metabolites nquag. Cov txheej txheem no feem ntau tshwm sim hauv daim siab thiab cuam tshuam nrog CYP450 enzyme system. Phenobarbital yog ib qho tshuaj sedative thaum ub uas tau siv dav hauv kev kho mob antiepileptic. Nws exerts nws cov nyhuv antiepileptic tsuas yog los ntawm kev txhim kho txoj haujlwm ntawm GABA A receptor, yog li txo qhov excitability ntawm neurons thiab tswj qhov tshwm sim ntawm qaug dab peg.
Tus nqi ntawm cov metabolism thiab excretion ntawm Primidone sib txawv nrog cov neeg sib txawv. Cov poj niam cev xeeb tub, cov neeg mob qaug dab peg, cov me nyuam mos, thiab cov neeg laus feem ntau muaj cov kab mob metabolic qeeb dua li cov neeg noj qab haus huv. Tsis tas li ntawd, ntau yam, xws li lub siab ua haujlwm thiab kev cuam tshuam ntawm lwm yam tshuaj, thiab lwm yam kuj tseem tuaj yeem cuam tshuam rau cov metabolic tus nqi ntawm Primidone.
4. Kev tso tawm:
Primidone thiab nws cov metabolites feem ntau yog tawm los ntawm lub raum. Ib nrab-lub neej ntawm Primidone yog 8-24 teev, thiab lub sij hawm excretion yuav txawv raws li tej yam xws li tus neeg mob lub raum ua hauj lwm thiab metabolic tus nqi. Hauv cov neeg mob uas lub raum tsis ua haujlwm, tus nqi ntawm kev tso tawm tuaj yeem txo qis, yog li ua kom cov ntshav plasma concentration ntawm cov tshuaj thiab cov kev pheej hmoo ntawm cov tshuaj lom.
Nyob rau hauv luv luv, Primidone yog ib qho tshuaj ntawm qhov ncauj, uas yog metabolized thiab tawm los ntawm daim siab metabolism thiab lub raum excretion. Nws nqus, faib, thiab tawm cov txheej txheem raug cuam tshuam los ntawm ntau yam, xws li cov yam ntxwv ntawm lub cev, tus nqi metabolic, thiab lub siab ua haujlwm. Nkag siab txog cov tshuaj pharmacokinetic ntawm Primidone yog qhov tseem ceeb heev rau kev tsim cov tshuaj tsim nyog thiab saib xyuas cov tshuaj ua tau zoo thiab kev pheej hmoo.
Keeb kwm ntawm Primidone qhov kev tshawb pom tau pib thaum xyoo 1940, thaum tus kws kho mob npe hu ua Schechter thawj zaug pom tias qhov sib xyaw no tuaj yeem muaj txiaj ntsig ntawm kev kho mob qaug dab peg thiab tshee.
Xyoo 1949, tus kws muag tshuaj Asmeskas thiab tus kws kho mob neuroscientist Sidney Udenfriend thiab lwm tus tau tsim cov Primidone thawj zaug, thiab pom tias nws muaj cov nyhuv sedative thiab anticonvulsant hauv cov tsiaj. Txij thaum ntawd los, Primidone pib nkag mus rau theem kev sim tshuaj, thiab thaum kawg tau lees paub tias muaj kev tswj hwm zoo ntawm yuav luag txhua hom mob vwm, thiab maj mam dhau los ua ib qho ntawm cov tshuaj tiv thaiv kab mob tseem ceeb.
Cov hauv qab no yog cov lus piav qhia ntxaws txog keeb kwm ntawm Primidone qhov kev tshawb pom:
1. Kev tshawb nrhiav thaum ntxov:
Primidone tau tsim los ntawm Sidney Udenfriend thiab cov npoj yaig thaum ntxov 1940s. Thaum lub sij hawm, lawv tab tom nrhiav cov tshuaj antiepileptic tshiab los kho cov kab mob neurological no. Qhov no yog ib txoj haujlwm nyuaj heev vim tias muaj ntau hom mob vwm thiab lawv teb txawv rau cov tshuaj sib txawv.
Thaum lub sijhawm tshawb nrhiav, Udenfriend tau siv cov tshuaj hu ua "promethazine" los tsim cov tshuaj tiv thaiv kab mob vwm tshiab. Nws pom tias cov tshuaj muaj cov tshuaj tiv thaiv kab mob thiab sedative hauv cov tsiaj, tab sis cov teebmeem tsis txaus siab heev.
Yog li Udenfriend thiab nws cov npoj yaig tau teeb tsa los tsim cov tshuaj promethazine zoo li thiab sim lawv. Ntawm lawv, Primidone yog ib qho ntawm cov tebchaw thaum kawg pom tias muaj cov nyhuv antiepileptic.
2. Thawj qhov kev sim tshuaj:
Xyoo 1949, Udenfriend et al. siv Primidone thawj zaug hauv tib neeg kev sim tshuaj ntsuam xyuas nws cov kev ua tau zoo ntawm kev qaug dab peg. Nws tau pom tias Primidone muaj txiaj ntsig zoo hauv kev tswj yuav luag txhua hom kev mob vwm nrog qee qhov kev mob tshwm sim.
Txawm li cas los xij, kev tshawb fawb nyob rau lub sijhawm ntawd tsuas yog txwv rau kev sim me me thiab cov ntaub ntawv xov xwm, thiab xav tau kev tshawb fawb ntxiv los ua pov thawj qhov ua tau zoo thiab kev nyab xeeb ntawm Primidone. Qee qhov kev tshawb fawb tau pom tias Primidone tuaj yeem muaj kev phiv ntau dua li lwm cov tshuaj tiv thaiv kab mob, xws li kiv taub hau, qaug zog, thiab kev xav tsis zoo.
Qhov no tau ua rau muaj kev txwv tsis pub siv Primidone, uas tsuas yog siv tau raws li kev soj ntsuam nruj thiab saib xyuas.
3. Kev tshawb nrhiav tom qab:
Ob peb xyoos tom ntej no, ntau tus kws tshawb fawb tau tshawb fawb ntxiv ntawm Primidone los ntsuas nws cov txiaj ntsig thiab kev nyab xeeb tiv thaiv kab mob vwm thiab tshee.
Qee qhov kev tshawb fawb tau pom tias Primidone muaj txiaj ntsig zoo hauv kev txo qis qhov tshwm sim ntawm qaug dab peg, thiab tuaj yeem ua haujlwm zoo dua rau cov neeg uas muaj qee yam mob vwm. Tsis tas li ntawd, Primidone kuj tau raug pov thawj tias siv los tswj qhov pib ntawm kev tshee, xws li kev tshee zoo ntawm Parkinson tus kab mob.
Txawm li cas los xij, kev phiv ntawm Primidone tseem yog ib qho kev txhawj xeeb tseem ceeb. Ntxiv nrog rau cov kev mob tshwm sim yav dhau los, cov kev mob tshwm sim hnyav kuj tau raug tshaj tawm, xws li leukopenia, lub siab ua haujlwm tsis zoo, thiab lwm yam. Cov kev tshawb pom no ua rau muaj kev txwv ntxiv rau kev siv Primidone.
Sij hawm dhau mus, lwm cov tshuaj tiv thaiv kab mob maj mam hloov Primidone. Txawm li cas los xij, Primidone tseem suav tias yog ib qho ntawm cov tshuaj zoo rau kev kho mob qaug dab peg thiab tshee, thiab tseem siv dav hauv qee qhov tshwj xeeb.
Saum toj no:
Primidone yog ib qho tshuaj tiv thaiv kab mob vwm thiab tiv thaiv kev tshee, tshwm sim hauv xyoo 1940, tsim los ntawm Sidney Udenfriend li al., thiab tau ua pov thawj nws cov txiaj ntsig kho mob rau qaug dab peg thiab tshee los ntawm kev sim tshuaj. Txawm li cas los xij, cov kev mob tshwm sim thiab kev txwv ntawm Primidone tau dhau los ua pom tseeb, ua rau lwm cov tshuaj tiv thaiv kab mob maj mam hloov nws. Txawm li cas los xij, Primidone tseem suav tias yog ib qho ntawm cov tshuaj tseem ceeb hauv kev kho mob qaug dab peg thiab tshee, muab cov neeg mob nrog kev xaiv kev kho mob zoo.