
epibatidine

epibatidine anedi chlorinated alcoloid, idhi ekuvadoran kappa "epidebates anthoni" mariyu "ameeregaa" jaatiki chendina vishapuurita dart kappala dwara sravistundi. dheenini zaan doubleu kanugonnaru. 1974loe dolly, conny 1992 varaku daani nirmaanam puurtigaa spashtam kaaledu. chlorinated aalkalaaydku epibatidine modati pariseelinchina udaaharana kaadaa anedi vivadaspadamga undhi, dolly sekarinchina parimita namuunaala nundi sammelanaanni nischayamgaa gurtinchadamlo savaalla kaaranamgaa. 1991loe adhika-resolution spectrometrini upayoginche samayaniki, dolly namuunaala nundi oka milligramula kante takkuva saram migili undhi, idhi kalushyam gurinchi aandolanalanu penchindi. adhe jaatiki chendina kappa yokka itara byaachla nundi namuunaalu epibatidine nuu ivvadamlo viphalamayyayi.
epibatidine vishapuuritam. nicotinic mariyu mascarinic acetylcholine graahakaalato sankarshana chendhe saamarthyam valla dheeni vishapuuritam avutundi. eee grahakaalu itara vidhulatho paatu baadhaakaramaina anubhoothula prasaaramlo mariyu kadalikalo palgontayi. epibatidine appudu timmiriki, chivariki pakshavaataaniki kaaranamavutundi. pakshavaatam swaasakosha addankini kaliginchinappudu motaadulu praanaantakam. modata, epibatidine oka aushadhamgaa upayogapadutundani bhaavinchaaru. ayithe, daani aamodayogyam kaani chikitsa suuchika kaaranamgaa, idhi sambhaavya chikitsa upayogaala kosam parisoedhana cheyabadatam ledhu.
charitra.
epibatidine nuu zaan doubleu kanugonnaru. 1974loe dolly. dolly mariyu sahodyogi charless myers sekarinchina "epipedobates anthoni" kappala charmam nundi idhi vaeru cheyabadindi. 1974 mariyu 1979 madhya, dolly mariyu myers eekvaadarlooni vividha pradaesaala nundi daadaapu 3000 kappala tokkalanu sekarinchaaru, vaati charmam nundi oka chinna injection vaari charmam nundi oka opiyaayidnu pooli unde elukalalo noppini tagginche (noppini tagginche) prabhavalanu kaligistundani kanugonnaru. daani saadhaarana paeru-anthony yokka visha baanam kappa-vaeta samayamlo dheenini sthaanikulu upayoginchaarani suuchimchinappatikii, 2000loe dolly raasina oka kaagitam kappala chuttoo sthaanika jaanapada kathalu ledhaa jaanapada aushadham ledani mariyu vaatini sthaanikulu ekkuvagaa praamukhyata laenivigaa bhaavinchaarani perkondi.
epibatidine yokka nirmaanam 1992loe spashtam cheyabadindi, eee prayatnaaniki "ii" addankigaa nilichindi. anthoni 1984loe iucn rakshita hodaanu pondindi. inca, eee kappalu cheralo penchinappudu mariyu penchinappudu vishanni utpatti cheyavu, endukante avi epibatidine nuu samslaeshanha cheyavu. itara vishapuurita dart kappala maadirigaane, vaaru badulugaa tama aaharam dwara daanini pondutaaru, aapai daanini vaari charmampai vaeru chestaaru. beatles, cheemalu, purugulu mariyu eegalu bahusha aahara vanarulu. 1976loe ecudarku tirigi velladam valla epibatidine utpatti cheyabadindani dolly mariyu charless gamaninchaaru, oka pradaesamloe, unna kappalu aevee epibatidine vanti alkalaydlanu utpatti cheyaledani vaaru kanugonnaru; aahara maargaalato konni pradaesaalaloo kappalu matrame eee kappalanu epibatidine utpatti cheyadaaniki anumatinchaayani vaaru kanugonnaru. eee ibbandulanu adhigaminchi, nirmaanam chivariki nirnayinchabadindi, mariyu epibatidine yokka modati samslaeshanha 1993loe puurtayimdi. appati nundi aneka itara samslaeshanha paddhatulu abhivruddhi cheyabaddaayi.
daani analgesic prabhavam kaaranamgaa, epibatidine nuu aushadhamgaa upayoginchadampai teevramaina aasakti undhi, endukante idhi opioid kaadani kanugonabadindi. dheeni ardham vyasanam bhayam lekunda dheenini upayoginchavacchu. ayithe, vishapuurita lakshanaalaku daariteese motaadu surakshitamgaa undataaniki chaalaa takkuvagaa unnanduna dheenini maanavulalo upayoginchalemani tvaralo kanugonabadindi.
samslaeshanha.
prakrutilo epibatidine saapeksha korata kaaranamgaa aneka mottam samslaeshanha margalu roopondinchabaddaayi.
epibatidine yokka nirmaanaanni kanugonna taruvaata, prayogasaalalo daanini samslaeshanha cheyadaaniki yaabhaiki paiga margalu roopondinchabaddaayi. modati nivedinchabadina udaaharanalo, tommidi-dasala prakriya padaarthaanni resmetga utpatti chestundi (dheeniki viruddhamgaa, sahajamgaa sambhavinche sammelanam (+)-ananciomer; (−)-ananciomer sahajamgaa sambhavinchadu). (+) mariyu (-) ananciomerlu samaanamaina analgesic mariyu vishapuurita prabhavalanu kaligi unnayani taruvaata nirdhaarinchabadindi. eee prakriya daadaapu 40 saatam digubadini istuu chaalaa utpaadakamgaa niroopinchabadindi.
chloronicotinaldehyde nundi praarambhamayye ej koori nivedinchina anancioselective samslaeshanha krinda vivarinchabadindih
corey paddhatitoe paatu, itara mukhyamaina paddhatulalo broka, huwang mariyu kollu, mariyu clayton mariyu regaon unnaayi.
synthetic analogues.
noppini nivaarinche prabhavalanu nirvahinche, conny vishapuuritam lekunda unde epibatin yokka nirmaana saaruupyaalanu kanugonadaaniki aneka vidhanalu prayatninchabaddaayi. udaaharanaku, abbat prayogasaalalu abt-594 thoo sahaa epibatidine yokka utpannaalanu utpatti chesaayi. abt-594 noppi avagahananu niyantrinche graahakaalato bandhinchadam dwara mariyu kandaraala-rakam nicotinic acetylcholine grahakaalu (natcher) daani pakshavaata prabhavanni tagginchadam dwara pakshavaataanni nivaarinchadam dwara noppini nivaarinche lakshanaalanu kaligi undhi. itara epibatidine analogues loe abt-418, epiboxidine mariyu vaati utpannaalu unnaayi. 7-ajanorbornenlo kriyaarahitam cheyani carbon yokka microbial hydroxylation upayoginchi epibatidine samslaeshanha 1999loe prachurinchabadindi.
rasayana nirmaanam.
epibatidine anedi nikotin maadirigaane nirmaanamtho kuudina piperidine pyridine. idhi oka hygroscopic jiddugala padaardham, idhi oka bays.
jeevasambandhamaina prabhavalu.
charya yokka yantraangam.
epibatidine rendu charya vidhaanaalanu kaligi untundih idhi nicotinic acetylcholine grahakaalu (natcher) ledhaa mascarinic acetylcholine grahakaalu (matcher) thoo bandhinchagaladu. pratyaekamgaa, epibatidine yokka analgesic lakshanam nicotinic graahakaala yokka α4/β2 uparakamtho bandhinchadam dwara jarugutundani nammutaaru. epibatidine kooda α3/β4 uparakamtho bandhistundi mariyu chaalaa takkuva sthaayilo α7 grahakaalu (α4/β2 kante 300 retlu takkuva anubandham) kandaraala nicotinic graahakaalaku anubandhaala rank arder αε> αγ> αδ.
nicotinic acetylcholine grahakaalu naraala kanaala post-synaptic porallo kanipistaayi. eee grahakaalu ayan gated chaanellaku oka udaaharana, ikkada ligand dwara bandhinchadam valana ayanlu poranu daatadaaniki veelugaa oka conformational maarpuku kaaranamavutundi. avi kendra mariyu paridheeya naadii vyavasthalo naraala prasaranni pracharam chestaayi. neurotransmitterlu eee graahakaalato bandhinchinappudu, ayan chaanallu teruchukuntaayi, idhi naa + mariyu ca2 + ayaanlanu pora antataa kadaladaaniki anumatistundi. idhi post-synaptic poranu vidhvamsam chestundi, signalnu pracharam chese charya saamarthyaanni prerepistundi. eee sanketam chivariki dopamine mariyu norpinefrine vidudalanu prerepistundi, phalitamgaa jeevipy antinosyseptive prabhavam untundi.
naacharku saadhaarana neurotransmitter acetylcholine. ayithe, itara padaarthaalu (epibatidine mariyu nikotin vantivi) kooda graahakamtho bandhinchagalavu mariyu okela kakapoyina, idhe vidhamaina pratispandananu prerepinchagalavu. grahaka uparakaanni batti, α4β2 uparakam vadda 0.05 nm nundi α7 uparakam vadda 22 nm varaku, epibatidine natures patla chaalaa ekkuva anubandhaanni kaligi untundi. nikotin kante anubandham mariyu samarthatha (anduvalla shakti kooda) chaalaa ekkuvagaa untaayi.
epibatidine yokka pakshavaata lakshanam kandaraala-rakam nicotinic graahakaalato bandhinchina tarvaata jarugutundi.
epibatidine yokka takkuva motaadu naacharlanu matrame prabhaavitam chestundi, endukante maacharla kante naacharlaku ekkuva anubandham untundi. ayithe, adhika motaadulu epibatidine nuu machaarsto bandhinchadaaniki kaaranamavutaayi.
epibatidine yokka (+)-mariyu (-)-ananciomerlu rendoo jeevasaastraparamgaa churukuga untaayi, mariyu rendoo naacharlaku saaruupya bandha sambandhaalanu kaligi untaayi, (+)-ananciomer matrame sahanamnu prerepinchadu. idhi marphin kante sambhaavya chikitsa prayojanam ayinappatikee, epibatidine clinical trialsloki pravesinchaledu endukante chaalaa chinna motaadulu kooda elukalaku praanaantakam.
lakshanaalu.
epibatidine aneka vishapuurita parinaamaalanu kaligi untundi. anubhavapuurvakamgaa niroopitamaina prabhavalalo splanknick saanubhootigala naraala utsarga mariyu perigina dhamani peedanam unnaayi. naraala utsarga prabhavalu epibatidine yokka takkuva motaadulo central nicotinic acetylcholine graahakaala agonism dwara paakshikamgaa madhyavartitvam cheyabadina antinocyceptionku kaaranamavutaayi; 5 microgram/kilolu. ayithe, adhika motaadulo, epibatidine pakshavaatam mariyu spruha kolpovadam, coma mariyu chivariki maranaaniki kaaranamavutundi. epibatidine yokka madhyastha praanaantaka motaadu (eldi50) 1.46 microgram/kilolu mariyu 13.98 microgram/kilola madhya untundi. idhi dioxin kante epibatidine nuu kontha ekkuva vishapuuritam chestundi (sagatu eldi50 22.8 microgram/kilolatho). daani vishapuurita ekagrata mariyu antinosyseptive ekagrata madhya chinna vyatyaasam kaaranamgaa, daani chikitsa upayogaalu chaalaa parimitam.
elukalapai chesina parisoedhanaloo, 5 microgram/kilola kante ekkuva motaadula epibatidine teesukovadam valla jeevipy motaadu-aadhaarita pakshavaatam prabhavam erpadindi. 5 microgram/kiloku paiga motaadulatoe, lakshanaalu adhika raktapotu (raktapotu peragadam), swaasakosha vyavasthalo pakshavaatam, muurchalu mariyu chivariki maranam. ayithe, takkuva motaadulu icchinappudu lakshanaalu teevramgaa marutayi. adhika motaadula pratikuula prabhavalu lekunda elukalu noppi mariyu vaedini nirodhinchagalavu.
aushadha shaastram.
epibatidine atyanta samarthavantamgaa injection dwara sareeramloki pravesistundi. inn vitro adhyayanalu epibatidine maanava sareeramlo jeevakriya cheyabadadani suuchistunnaayi.
sareeram nundi clearance maargampai kooda prastutam chaalaa takkuva samacharam undhi. sareeramloki pravesinchina 30 nimishala tarvaata medadulo garishta ekagrata cherutundi.
sambhaavya vaidya upayogaalu.
paina perkonna vidhamgaa epibatidine adhika analgesic saktini kaligi untundi. adhyayanalu idhi marphin kante kaneesam 200 retlu ekkuva saktini kaligi undani chuupistunnaayi. eee sammelanam vyasanaparudainadi kaadu ledhaa alavaatu kaliginchaledu kabatti, noppini tagginche mandugaa marphin sthaanamlo unchadam chaalaa asajanakamga untundani modatlo bhaavinchaaru. ayithe, chikitsa ekagrata visha saandrataku chaalaa daggaragaa untundi. dheeni ardham, chikitsa motaadu (5 microgram/kejee) vadda kooda, konni epibatidine mascarinic acetylcholine graahakaalato bandhinchi, adhika raktapotu, broadycardia mariyu kandaraala paresis vanti pratikuula prabhavalanu kaliginchavacchu.
noppi nirvahanalo bangaaru pramaanamtho poliste, marphin, epibatidine noppi-upasamana prabhavanni praarambhinchadaaniki 2.5 microgram/kiloku matrame avasaramavutundi, adhe prabhaavaaniki sumaru 10 milligramulu/kiloku marphin (4,000 retlu samarthatha) avasaram.) prastutam, epibatidine prabhavalapai praathamika parisoedhana matrame inca nirvahinchabadindi; eee samayamlo vislaeshanha kosam eee aushadhaanni elukalaku matrame ivvabadindi.
virugudu.
epibaatidinku virugudu mcamillamine, idhi nicotinic acetylcholine grahaka virodhi, idhi empika kaanidi mariyu pootii laenidi. mcamillamine yokka (+) mariyu (-) ananciomerlu rendoo samarthavantamgaa kanipinchaayi mariyu rendoo nicotinic acetylcholine graahakaalaku oke anubandhaanni kaligi unnaayi.