
tolcapone

tasmar brand paerutoe vikrayinche tolcapone, parkinsons vyaadhi (pidi) chikitsaku upayoginche aushadham. idhi catecol-"oo"-methyl transferes (comt) enjaim yokka empika chesina, saktivantamaina mariyu reversible nitrocatecol-rakam nirodhakam. idhi gananeeyamaina kaaleya vishapuuritatanu pradarsinchindi, idhi aneka deshaalalo marketing adhikaaraalanu nilipiveyadaaniki daariteesindi.
maroe nitrocatecol comt inhibitor ayina entacapontho poliste, tolcaponeku ekkuva sagam jeevitam untundi (2.9 gantalu verses. 0.8 gantalu) mariyu rakta-medadu avarodhaanni baga chochukupogaladu, kendra naadii vyavasthalo mariyu anchulo panichestundi. ayithe, entacapone kaaleyaaniki takkuva vishapuuritam.
vaidya upayogaalu.
parkinsons vyaadhi chikitsalo tolkaponnu levodopa/carbidopa ledhaa levodopa/benserazide aushadhaalaku anubandhamgaa upayogistaaru. levodopa anedi dopamineku oka utpatti, idhi parkinson lakshanaalanu taggistundi; carbidopa mariyu benserazide anevi sugandha-amaino aamlam decarboxylase (aadc) nirodhakaalu.
tolcapone ivvakunda, levodopa yokka prayojanakaramaina prabhavalu marinta twaragaa ksheenistaayi, phalitamgaa motaru hecchutaggulaku daariteestundi.
vyatiraeka suuchanalu.
tolkaponnu fenelgine ledhaa tranilcypromine vanti naan-selective monoamine accidase inhibitorsto kalapadam viruddhamgaa untundi. kaaleya vyaadhulu ledhaa perigina kaaleya enjaimlu unnavaariki tolcapone kooda vyatiraekam.
dushprabhaavaalu.
aushadham yokka upayogaanni parimitam chese gananeeyamaina kaaleya vishapuuritatanu (hepatotoxicity) tolcapone pradarsinchindi. entacapone anedi oka pratyaamnaayam, endukante idhi marinta anukuulamaina vishapuurita profilenu kaligi untundi.
hepatotoxicity anedi perigina sthaayi transaminises kuu sambandhinchinadi kaavacchu, conny enjaim sthaayilanu paryaveekshistunnappudu mundugaa unna kaaleya paristhitulu laeni vaariki takkuva pramaadam undani adhyayanalu choopinchaayi. spashtamaina yantraangam edhee chikkukoledu, conny aakseekarana phosphorylation yokka kalapadam kaaranamgaa asaadhaarana mitochondrial swaasakriyatoe dheeniki edainaa sambandham undani oohinchabadindi. 
itara dushprabhaavaalu jeerna lakshanaalatoo sahaa dopaminergic karyakalapala perugudalanu pariganistaayi. tolcapontho chikitsa cheyadam valla diaskinitia vachhe pramaadam ledhaa podigimpu pramaadam untundi; levodopa motaadunu tagginchadam dwara dheenini nirodhinchavacchu. idhi sambhavistundi endukante tolcapone yokka paripalana phalitamgaa parkinson lakshanaalanu prerepinche stritumlo biological methyl daata yokka-adenosyl-methionin (saam) perukupotundi.
jeerna lakshanaalalo vikaram mariyu atisaaram unnaayi; marinta dopaminergic dushprabhavalalo orthostatic hypotension, noru endipovadam, chemata pattadam mariyu maikamu untaayi. tolcapone kante tolcapone marinta teevramaina virechanaalaku kaaranamavutundi; adhyayanaalalo chikitsa raddu cheyadaaniki idhi atyanta saadhaarana kaaranam. moothramlo visarjinchabade pasupu tolcapone metabolites nundi moothram rangu maarutundi mariyu idhi pramaadakaram kaadu.
paraspara charyalu.
dopamine sthaayila perugudala anedi kaavalasina paraspara charya ayithe, tolcapone siddhaantaparamgaa comt dwara jeevakriya cheyabadina itara aushadhaala sthaayilanu kooda penchutundi, veetilo eah. dii. sii inhibitors carbidopa mariyu benzerazide, alaage methyldopa, dobutamine, apomorphine, adrenaline mariyu isoprenaline vantivi unnaayi. adhyayanaalalo, benzerazidetho swalpa paraspara charya kanipinchindi, conny carbidopatho kaadu. eee aushadhaala samuuhamtoe itara paraspara charyalu adhyayanam cheyabadaledu. monoamine oxidase (maavo) inhibitors mariyu noradrinaline reaptake inhibitors vanti catecolamine saandratalanu penche mandulatho sambandhita rakamaina saiddhaantika paraspara charyalu untaayi; ivi aacharanalo swalpa prabhavalanu matrame chupayi. naan-selective" maavo inhibitorsto kalayika pramaadakaram kaavacchu.
kaaleya enjaim saip2sii9 thoo daani anubandham kaaranamgaa, eee enjaim dwara jeevakriya cheyabadutunna aushadhaalato paraspara charyalu kooda saadhyame, conny asambhavam. adhyayanaalalo 2sii9 uparitalamaina tolbutamidetho etuvanti paraspara charya gamaninchabadaledu.
aushadha shaastram.
charya yokka yantraangam.
tolcapone levodopatho sahaa moodu katekolamainlalo edainaa kante ekkuva anubandhaanni kaligi unna anchu mariyu kendra naadii vyavastha (cns) rendintiloonuu comt yokka utpreraka pradaesaaniki empikagaa mariyu tirogamanamgaa bandhistundi. tadwara idhi anchuna comt dwara levodopa yokka 3-"oo"-methylation nirodhistundi, idhi 3-"oo"-methyldopanu utpatti chestundi, idhi rakta-medadu addankini daatadaaniki levodopatho potipade pradhana jeevakriya. nirvahinchabadutunna levodopa ekkuva bhaagam cnsku cherukuntundi. adanamgaa, dopaminega marchabadina tarvaata ippatike cnsku cherukunna levodopa, tolcapone comt charyanu nirodhinchinappudu twaragaa ksheeninchadu. anduvalla, tolcapone jeeva labhyatanu meruguparustundi mariyu levodopa mariyu taruvaata cns nundi dopamine yokka tolagimpunu taggistundi.
nirodha sthiraamkam kii (2.5 nm) dwara suchinchabade tolcapone yokka bandham anubandham yokka balaanni enjaim mariyu nirodhakam sanklishta gtsastraniki viyojana sthiraamkamgaa bhaavinchavachchu. garishta utpreraka charya tolcapone yokka saamarthyaanni suuchistumdi (vimax = 58.4 pmol/minemg).
pharmacokinetics.
tolcapone pegu nundi 85 saataaniki twaragaa grahinchabadutundi. idhi 65 saatam sampoorna jeeva labhyatanu kaligi undhi, idhi aahaaramto teesukunnappudu koddigaa taggutundi. eee padaardham sumaru rendu gantala tarvaata atyadhika rakta plasma saandratalaku cherukuntundi. raktapravaahamlo unnappudu, idhi daadaapu puurtigaa (> 99.9%) plasma proteinlaku, pradhanamgaa albuminku kattubadi untundi. pradhana nishkriyaatmaka dasha glucuronidation; itara prakriyalu comt dwara methylation, saip3eah4 dwara hydroxylation mariyu saip2eah6 dwara tadupari carboxylic aamlaaniki aakseekarana, mariyu bahusha tadupari acetylationtho amainku taggimputoe oka chinna maargam.
tolcapone yokka ardha-jeevitam rendu nundi moodu gantalu, pampinhee parimaanam (vidi) 0.3 ell/kejee (sagatu 70 kilola vyaktilo 21 ell). 60 saatam gvakriyalu moothram dwara mariyu 40 saatam malam dwara visarjinchabadataayi. kevalam 0.5 saatam mandulu matrame moothram dwara maarani roopamlo visarjinchabadataayi.
sareeramlo 99 saatam tolcapone monoanianic roopamlo untundi endukante saareeraka pihech 7.4. tolcapone rakta-medadu avarodhaanni rendu itara nitrocatecols, nitecapone mariyu entacapone kante chaalaa merugga chochukupotundi, endukante daani aarr-pratyaamnaayam kaaranamgaa idhi adhika lipophilicityni kaligi untundi. vibhajana gunakaalu raktam-medadu addankini daate anuvu saamarthyaanni lekkistaayi. tolcapone, naitkapon mariyu entacopone kosam logpids = 0.20,-1.4,-04 varusaga. eee sandarbhamlo vibhajana gunakaalu 1,2-dichloroethane/hetch2oo draavanamloo kolustaaru, idhi anuvulu ayaneekaranam roopamlo undataaniki kaaranamaindi. eee charge cheyabadina anuvulu rakta-medadu avarodhamlo elaa pravesistaayanedaaniki prastuta vivarana ledhu.
rasayana shaastram.
tolcapone anedi teevramaina pasupu, vaasana laeni, chedhu ruchi, hygroscopic kaani, spatikaakaara sammelanam, dheeni saapeksha paramaanu dravyarashi 273.25 g/mol. idhi neetilo mariyu aamlalalo aacharanatmakamgaa karaganidi, conny 0.01 mea. jaleeya sodiyam hydroxide draavanamloo karugutundi. rendu phenyl samuuhaalaku p "k" a viluvalu 4.5 mariyu 10.6; mariyu garishta shoshana 268 nm (0.1 mea hydrochloric aamlam/ithanaallo) vadda untundi. dheeni rasayana paeru 3,4-dihydroxy-4 '-methyl-5-nitrobenzophenone.
samslaeshanha.
2008loe pratipaadinchabadina tolcapone samslaeshanha, madhya grignard praticharyatho praarambhamavutundi. 
3-benzyloxy-4-methoxybenzaldehyde mariyu "pii"-tolile magnitium bromide. aaa vidhamgaa utpatti ayye alkahal sodiyam "tii"-beautoxide upayoginchi keatonga maarchabadutundi. ammonium formate samakshamlo palladium-utpreraka hydrogenation dwara benzyl rakshana samuuham tolaginchabadutundi. benzyl eethar cheelikalo musugu lekunda hydroxyl samuuham prakkane unna 5-sthaanam vadda nitro samuuham pravesapettabadutundi. utpatti alkahalnu utpatti cheyadaaniki aluminium chloridenu upayoginchi methoxy samuuham cheelikatho samslaeshanha mugustundi.
charitra.
tolcapone aagashtu 1997loe european marketloki pravesapettindi, aaa taruvaata marchi 1998loe united states marketloki pravesapettindi. tolcapone icchina naluguru vyaktulalo kaaleya vishapuuritam nivedinchabadindi, mugguru vyaktulu samasyala kaaranamgaa maraninchaaru. paryavasanamga, tolcapone yokka marketing adhikaram december 1998 nundi augustu 2004 varaku nilipiveyabadindi, appudu adhi ettiveyabadindi. 1998 navambarulo, tolkaponnu tayaaru chesina company swachchandamgaa eee aushadhaanni market nundi tolaginchindi. aaa tarvaata augustu 2009loe adhikaram punaruddharinchabadindi. <reifer paeru = "emia/474722/2009"> </reifer>
nivedinchabadina samasyala phalitamgaa, yuu.ess. phud und drugg administration (fda) november 1998loe parkinsons vyaadhiki suuchimchina tolcapone paryaveekshanhanu niyantrinche lakshyamtho tolcapone mariyu label savaranala kosam block baaks heccharikanu jaarii chesindi. aneka itara deshaalu market nundi tolkaponnu upasamharinchukunnaayi; fibravari 1999loe australia, april 1999loe bulgaria, november 1998loe island, december 1998loe lithuvania.
parisoedhana.
aushadham kaaryaacharananu kaligi undavacchani soochinche praathamika dayta kaaranamgaa, yuu.ess. 2013loe eff. dii. eah. transthyretine family amyloidosis (eah. tii. aarr) chikitsanu lakshyamgaa chesukuni chesina adhyayanaalalo tolcapone "anaadha aushadha hodha" manjuru chesindi. ayithe, eee vyaadhi chikitsa kosam tolcapone fda aamodinchabadaledu.

