
grahaka virodhi

grahaka virodhi anedi oka rakamaina grahaka ligand ledhaa aushadham, idhi grahakanni agonist laaga sakriyam cheyakunda daaniki bandhinchadam mariyu nirodhinchadam dwara jeeva pratispandananu nirodhistundi ledhaa taggistundi. antiganst drugs anedi receptor proteinla sahaja operationlo jokyam chesukuntaayi. vaatini konnisaarlu blockers anie pilustaaru; udaaharanalalo alfa blockers, beata blockers mariyu calcium chaanal blockers unnaayi. aushadha saastramlo, satruvulaku anubandham untundi conny vaati cognit graahakaalaku samarthatha undadu, mariyu bandham paraspara charyaku antaraayam kaligistundi mariyu graahakaala vadda agonist ledhaa inverse agonist paniteerunu nirodhistundi. pratyarthulu kriyaaseela pradaesaaniki ledhaa graahakampai alosteric pradaesaaniki bandhinchadam dwara vaari prabhavalanu madhyavartitvam chestaaru, ledhaa vaaru grahaka karyakalapala yokka jeeva niyantranalo saadhaaranamgaa paalgonani pratyaekamaina bandhinche pradaesaalaloo sankarshana chendavacchu. virodhi-graheeta samudaayam yokka deerghaayuvunu batti virodhi karyakalapalu tiragalenivi ledhaa tirigi marchalenivi kaavacchu, idhi pratigaa, virodhi-graheeta bandham yokka swabhaavampai aadharapadi untundi. aushadha vyatiraekulaloo ekkuva mandhi grahakaalapai nirmanatmakamga nirvachinchina binding saitla vadda antarjanita ligandlu ledhaa uparitalaalato pootii padatam dwara vaari saktini saadhistaaru.
vyutpatti.
aushadha padaalaloo aangla padam virodhi greeku padamaina ἀνταγωνιστις nundi vachindi-"virodhi", "pratyarthi, pootiidaaru, pratinaayaka, satruvu, pratyarthi", idhi "vyatiraeka" ("vyatiraekamgaa") mariyu "agonijestay" ("bahumati kosam pootii padatam") nundi udbhavinchindi. 20va sataabdamloo american jeevasaastravetta bailey edgren satruvulanu kanugonnaru.
grahakaalu.
jeevarasaayana grahakaalu anevi pedda protein anuvulu, ivi harmon ledhaa aushadham vanti ligand yokka bandham dwara sakriyam cheyabadataayi. grahakaalu pora-kattubadi, kana uparitala grahakaalugaa ledhaa kana lopala mitochondriantho sahaa anhu grahakaalu vanti kanaantara grahakaalugaa undavacchu. grahakam mariyu daani ligand madhya samayojaneeyamaina paraspara charyala phalitamgaa, graahakampai bandhinche pradaesam anie piluvabade pradaesaalaloo bandham erpadutundi. oka grahakam vividha ligandla kosam okati ledhaa anthakante ekkuva binding saitlanu kaligi undavacchu. graahakampai kriyaaseela pradaesaaniki bandhinchadam anedi grahaka kriyaaseelatanu neerugaa niyantristundi. allosteric binding saitlalo vale, graahakampai itara saitlaku ligandnu bandhinchadam dwara kooda graahakaala karyakalapalanu niyantrinchavacchu. agonist-prerita pratispandanalanu nivaarinchadam dwara grahaka paraspara charyala dwara satruvulu tama prabhavalanu madhyavartitvam chestaaru. kriyaaseela pradaesaaniki ledhaa alosteric pradaesaaniki kattubadi undatam dwara idhi saadhinchavachchu. adanamgaa, pratyarthulu vaari prabhavalanu chuupadaaniki grahaka karyakalapala yokka jeeva niyantranalo saadhaaranamgaa paalgonani pratyaekamaina binding saitlalo sankarshana chendavacchu.
virodhi" anae padam modata aushadha prabhaavaala yokka vividha profilenu vivarinchadaaniki roopondinchabadindi. grahaka virodhi yokka jeevarasaayana nirvachananni 1950laloe arians mariyu stephenson pravesapettaaru. grahaka virodhi yokka prastuta aamodinchabadina nirvachanam grahaka occupancy namuunaapai aadharapadi untundi. idhi oke grahakam vadda vyatiraeka kaaryakalaapaalato unna sammelanaalanu matrame pariganaloki teesukoovadaaniki vyatiraekata yokka nirvachananni kudistundi. agonistlu graahakamtho bandhinchadam dwara oke cellular pratispandananu "aann" chestaarani bhaavinchaaru, tadwara kanamlo maarpu kosam jeevarasaayana yantraamgaanni praarambhinchaaru. agonist nundi grahakanni 'nirodhinchadam' dwara pratyarthulu aaa pratispandananu 'aapiveyaalani' bhaavinchaaru. eee nirvachanam saareeraka satruvulaku kooda upayogamlo undhi, saareeraka charyalanu vyatirekinche padaarthaalu, conny ververu graahakaala vadda panicheestaayi. udaaharanaku, histamine hetch1 grahakam vadda vasodilation dwara dhamanula ottidini taggistundi, ayithe adrenaline alfa-adrenergic grahaka kriyaaseelata dwara madhyavartitvam vahinchina vasoconstriction dwara dhamanula ottidini penchutundi.
aushadha-prerita grahaka kriyaaseelata mariyu grahaka siddhaantam yokka yantraangam mariyu grahaka virodhi yokka jeevarasaayana nirvachanam gurinchi mana avagahana abhivruddhi chendutune undhi. receptor activation yokka rendu-rashtra namuunaalu madhyantara conformational sthithulatho bahula-rashtra namuunaalaku maargam chupayi. functional selectivityni kanugonadam mariyu ligand-nirdishta grahaka conformations sambhavistaayi mariyu vividha rendava sandesha vyavasthalatho graahakaala paraspara charyanu prabhaavitam chestayani ardham, mandulanu grahakam yokka konni diguva vidhulanu sakriyam cheyadaaniki roopondinchavacchu, conny itarulu kaadu. dheeni ardham samarthatha vaastavaaniki aaa grahakam ekkada vyakteekarinchabadutunda daanipai aadharapadi undavacchu, grahakam vadda samarthatha anedi aushadham yokka grahaka-swatantra lakshanam anae abhiprayanni maarustundi.
pharmacodynamics.
samarthatha mariyu shakti.
nirvachanam prakaram, satruvulu vaaru bandhinche grahakalanu sakriyam cheyadaaniki etuvanti saamarthyaanni pradarsincharu. pratyarthulu grahakanni sakriyam chese saamarthyaanni konasagincharu. ayithe, okasari bandhinchabadinappudu, satruvulu agonistlu, inverse agonistlu mariyu pakshika agonistula paniteerunu nirodhistaaru. functional virodhi madimpulalo, oka motaadu-pratispandana vakrata oka agonist yokka kaaryaacharananu tippikottadaaniki satruvula saandratala shreni yokka saamarthyam yokka prabhavanni kolustundi. virodhi yokka shakti saadhaaranamgaa daani "sagam garishta nirodhaka ekagrata" (i.ii., ii. sii. 50 viluva). oka agonist yokka garishta jeeva pratispandana yokka sagam nirodhakatanu velikiteese avasaramaina virodhi yokka yekagratanu nirnayinchadam dwara icchina virodhi kosam dheenini lekkinchavacchu. aisi 50 viluvanu spashtam cheyadam anedi aushadhaala saamarthyaanni saaruupya prabhaavaalato poolchadaaniki upayogapadutundi, ayithe rendu aushadha satruvulu utpatti chese motaadu-pratispandana vakratalu okela undaali. IC50 entha takkuvagaa unte, virodhi yokka shakti antha ekkuvagaa untundi, mariyu garishta jeeva pratispandananu nirodhinchadaaniki avasaramaina aushadham yokka gaadata antha takkuvagaa untundi. mandula takkuva saandrata takkuva dushprabhaavaalato mudipadi undavacchu.
anubandham.
daani binding sait (kii) kosam virodhi yokka anubandham, i.ii. graahakamtho bandhinche daani saamarthyam, agonist karyakalapala nirodham yokka vyavadhini nirnayistundi. shilled regression upayoginchi ledhaa cheng-prusoff sameekaranaanni upayoginchi radioligand binding adhyayanaalalo pootii satruvula kosam virodhi yokka anubandhaanni prayogaatmakamgaa nirnayinchavacchu. shilled regressionu vyatiraekata yokka swabhaavaanni nirnayinchadaaniki upayoginchavacchu, endukante idhi pootii ledhaa pootii laenidigaa praarambhamavutundi mariyu kii nirnayam upayoginchina agonist yokka anubandham, samarthatha ledhaa ekagrata nundi swatantramgaa untundi. ayithe, samathoulyaanni cherukovadam mukhyam. samathoulyaanni cherukovadampai grahaka sunnitatvam yokka prabhavalanu kooda parigananaloki teesukoovaali. ayan chaanellanu nirodhinche pootii neuromuscular-blocking agentlalo alaage antagonising agonist binding vanti rendu ledhaa anthakante ekkuva prabhavalanu pradarsinche pratyarthula anubandha sthiraamkaanni shilled regressionu upayoginchi vislaeshimchalaemu. shilled regression anedi motaadu nishpattilo maarpunu polchadam, motaadu pratispandana vakrarekhapai nirnayinchina vidhamgaa pootii virodhi samakshamlo isi 50 thoo poliste oka agonist yokka isi 50 nishpatti matrame. pareekshalo upayoginche vyatiraekula mottaanni marchadam valla motaadu nishpattini maarchavacchu. shilled regressionlo, oka plaatlu logg (motaadu nishpatti-1) thoo, vyatiraekula saandratala shreni kosam vyatiraekula logg saandratatoe tayaaru cheyabadataayi. anubandhaanni ledhaa kii antey regression plaat meeda x-akshanni kattirinche rekha. ayithe, shilled regressiontho, cheng-prusoff sameekaranam nundi kii viluvalanu pondadaaniki upayoginche prayogaalalo virodhi ekagrata bhinnamgaa untundi, agonist saandratalu bhinnamgaa untaayi. pootii agonistlu mariyu pratyarthula patla anubandham anedi pootii nirodham samayamlo sambhavinche IC50 looni maarpu nundi kii (virodhi kosam anubandha sthiraamkam) nuu lekkinchadaaniki upayoginche cheng-prusoff karakam dwara sambandham kaligi untundi. cheng-prusoff karakam pootii satruvulachae utpatti cheyabadina nirodhampai graheetaku agonist ekagrata mariyu agonist anubandhaanni marchadam yokka prabhavanni parigananaloki teesukuntundi.
rakalu.
pootii.
pootii satruvulu antarjanita ligand ledhaa agonist vale adhe binding sait (kriyaaseela sait) vadda graahakaalato bandhistaaru, conny grahakanni sakriyam cheyakunda. graheetapai oke bandhinche pradaesam kosam agonistlu mariyu satruvulu "pootii" padataaru. okasari bandhinchina tarvaata, oka virodhi agonist bindingnu addukuntadu. virodhi yokka taginanta saandratalu binding saitla nundi agonistnu sthaanabhramsham chestaayi, phalitamgaa grahaka kriyaaseelata takkuva frequenseeki daariteestundi. grahakam yokka kaaryaacharana sthaayi sait kosam prati anuvu yokka saapeksha anubandham mariyu vaati saapeksha saandratala dwara nirnayinchabadutundi. pootii agonist yokka adhika saandratalu agonist aakraminche graahakaala nishpattini penchutaayi, adhe sthaayi binding sait occupancini pondadaaniki virodhi yokka adhika saandratalu avasaram. pootii satruvulanu upayoginchi kriyaatmaka madimpulalo, garishta pratispandanalo etuvanti maarpu lekunda agonist motaadu-pratispandana vakrarekhala samaantara kudi vaipuku maarpu gamaninchabadutundi.
pootii satruvulu mandula karyakalapalanu nivaarinchadaaniki mariyu ippatike viniyoginchina mandula prabhavalanu tippikottadaaniki upayogistaaru. heraine ledhaa marphin vanti aushadhaala valla kalige opioid adhika motaadunu tippikottadaaniki naloxone (narcon anie kooda pilustaaru) nuu upayogistaaru. adevidhamgaa, aaroo 15-4513 anedi madyaaniki virugudu mariyu flumagenil anedi benzodiazipainlaku virugudu.
pootii satruvulu vaari grahaka protein lakshyaalato elaa sankarshana chendutarane daanipai aadharapadi, tirigi pondagalige ("adhigaminchadagina") ledhaa tirigi pondaleni ("adhigaminchaleni") pootii satruvulugaa upa-vargeekarinchabaddaaru. naan-covalent intermolecular forces dwara bandhinche reversible antagonists, chivariki receptor nundi vidipotaayi, receptornu mallee bandhinchadaaniki veelu kalpistundi. tirigi pondaleni satruvulu samayojaneeya antar paramaanu saktula dwara bandhistaaru. sthaanika vaataavaranamloo samayojaneeya bandhaalanu vichchinnam cheyadaaniki taginanta uchita shakti lenanduna, bandham tappanisarigaa "saasvatamainadi", antey grahaka-virodhi sanklishtata eppatikee vidipodu. tadwara grahakam sarvavyaapti chendhi naasanam ayye varaku saasvatamgaa vyatiraekamgaa untundi.
pootii laenidi.
pootii laeni virodhi anedi adhigaminchaleni virodhi rakam, idhi rendu margallo okadaanilo panichestundihi grahakam yokka alosteric saitku bandhinchadam dwara ledhaa grahakam yokka kriyaaseela saitku tirigi maarchaleni vidhamgaa bandhinchadam dwara. modati ardham iufer dwara praamaanikam cheyabadindi, mariyu idhi virodhini "alosteric virodhi" anie pilavadaaniki samanam. eee rendu drugvishayaalalo satrutvam yokka vidhanam bhinnamgaa unnappatikee, rendintinee "pootii laenivi" anie pilustaaru endukante prati okkati yokka tudi phalitaalu kriyaatmakamgaa chaalaa pooli untaayi. pootii satruvula maadirigaa kakunda, idhi garishta pratispandananu saadhinchadaaniki avasaramaina agonist mottaanni prabhaavitam chestundi, conny aaa garishta pratispandana parimaanaanni prabhaavitam cheyadu, pootii laeni satruvulu yea mottamlo agonist ayina saadhinchagala garishta pratispandana parimaanaanni taggistaaru. eee aasti vaariki "pootii laenidi" anae paerunu sampaadistundi, endukante entha agonist unnaa vaati prabhavalanu tiraskarinchalemu. pootii laeni pratyarthula kriyaatmaka madimpulalo, agonist motaadu-pratispandana vakrarekhala yokka garishta pratispandana yokka niraasa, mariyu konni sandarbhaallo, kudi vaipuku maarpulu utpatti avtayi. grahaka nilva (vidi grahakaalu anie kooda pilustaaru) phalitamgaa kudi vaipuku maarpu sambhavistundi mariyu eee nilva ksheeninchinappudu matrame agonist pratispandana nirodham sambhavistundi.
kriyaaseela pradaesam mariyu virodhi madhya bandham tirigi pondalenidi ledhaa dadapuga unte grahakam yokka kriyaaseela pradaesaaniki bandhinche virodhini "pootii laenidi" anie antaaru. pootii laeni" anae padam yokka eee upayogam aadarsamgaa undakapovachhu, ayithe, "tirigi maarchaleni pootii satrutvam" anae padaanni kooda adhe drugvishayaanni vivarinchadaaniki upayoginchavacchu, endukante krinda charchinchina "pootii laeni satrutvam" yokka rendava ardhamtho gandaragolam kaliginche avakaasam lekunda.
pootii laeni satruvula" yokka rendava roopam alosteric sait vadda panichestundi. eee satruvulu agonist nundi pratyaekamaina binding saitku bandhistaaru, itara binding sait dwara aaa receptorku tama charyanu amalu chestaaru. kriyaaseela pradaesamloe bandhinchadaaniki vaaru agonistulatho potipadaru. agonist bandhinchina tarvaata grahaka kriyaaseelataku avasaramaina graahakamlo anukuula maarpulanu bandhinchina satruvulu nirodhinchavacchu. cyclothiazide mglur1 grahakam yokka tiragagalige pootii laeni virodhigaa panichestundani choopabadindi.
pootii laenidi.
pootii laeni satruvulu pootii laeni satruvula nundi bhinnamgaa untaaru, endukante vaaru pratyeka alosteric binding saitku bandhinche mundu agonist dwara grahaka kriyaaseelata avasaram. eee rakamaina satrutvam oka gathi profilenu utpatti chestundi, dheenilo "adhe mottamlo virodhi agonist yokka takkuva saandratala kante agonist yokka adhika saandratalanu baga nirodhistundi". algimers vyaadhi chikitsalo upayoginche memantine, nmda graahakaaniki pootii laeni virodhi.
nissabda satruvulu.
nissabda satruvulu anevi pootii grahaka satruvulu, ivi grahakanni sakriyam cheyadaaniki sunna antargata karyakalapalanu kaligi untaayi. vaaru nijamaina satruvulu, kabatti maatlaadataaniki. puurtigaa kriyaarahita satruvulanu balaheenamaina pakshika agonistlu ledhaa viloma agonistula nundi vaeru cheyadaaniki eee padam srushtinchabadindi.
pakshika agonistlu.
pakshika agonistlu icchina grahakam vadda, garishta grahaka occupancy tarvaata avi velikiteese kriyaatmaka pratispandana yokka vaisaalyamlo bhinnamgaa unde mandulugaa nirvachinchabaddaaru. vaaru agonistlu ayinappatikee, pakshika agonistlu puurti agonist samakshamlo pootii virodhigaa vyavaharinchavacchu, endukante idhi grahaka occupancy kosam puurti agonistho pootiipadutumdi, tadwara puurti agonistho matrame gamaninchina daanitoe poliste grahaka kriyaaseelataloo nikara taggudalanu utpatti chestundi. vaidyaparamgaa, vaati upayogam lopabhuishta vyavasthalanu merugupariche saamarthyam nundi teesukobadindi, adhe samayamlo adhika kaaryaacharananu nirodhistundi. receptornu adhika sthaayi pakshika agonist kuu bahirgatam cheyadam valla daani saadhaarana agonist adhika ledhaa takkuva sthaayilalo unnaa, adhi sthiramaina, balaheenamaina sthaayi kaaryaacharananu kaligi undela chestundi. adanamgaa, pakshika agonism saktivantamaina puurti agonistlu ledhaa satruvulaku padepade bahirgatamaina tarvaata tarachugaa abhivruddhi chendhe anukuula niyantrana yantraamgaalanu nirodhistundani soochinchabadindi. ii.zii. buprenorphine, micro-opioid grahakam yokka pakshika agonist, balaheenamaina marphin lanty kaaryaacharanatoo bandhistundi mariyu noppi nirvahanalo analgesicga mariyu opioid aadharapadatam chikitsalo methadoneku pratyamnaayamgaa vaidyaparamgaa upayoginchabadutundi.
viloma agonistlu.
viloma agonist virodhi maadirigaane prabhavalanu kaligi undavacchu, conny diguva jeeva pratispandanala yokka pratyaekamaina samitini kaligistundi. antargata ledhaa besal charyanu pradarsinche constitutivga kriyaaseela grahakaalu inverse agonistulanu kaligi undavacchu, ivi classical virodhi vanti binding agonistula prabhavalanu nirodhinchadame kakunda grahakam yokka besal charyanu kooda nirodhistaayi. gatamlo vyatiraekulugaa vargeekarinchabadina aneka mandulu ippudu inverse agonistulugaa tirigi vargeekarinchabadatam praarambhinchaayi, endukante constitutive active receptors kanugonabaddayi. histamine hetch1 graahakaalaku vyatiraekulugaa modata vargeekarinchabadina antihistaminelu viloma agonistulugaa tirigi vargeekarinchabaddaayi.
tirigi vachhe saamarthyam.
chaalaa mandhi satruvulu tiragagalige satruvulu, chaalaa mandhi agonistula maadirigaane, grahaka-ligand kinetics dwara nirnayinchabadina raetla vadda grahakanni bandhinchi, vidadeestaaru.
tirigi maarchaleni pratyarthulu grahaka lakshyamtho samayojaneeyamgaa bandhistaaru mariyu saadhaaranamgaa, tolaginchabadaru; virodhi prabhaavaala vyavadhilo grahakanni nishkriyam cheyadam anedi grahaka turnover raetu, kotta graahakaala samslaeshanha raetu dwara nirnayinchabadutundi. phenoxibenzamine anedi tirigi maarchaleni alfa blackerku oka udaaharana-idhi saasvatamgaa α adrenergic graahakaalato bandhistundi, adrenaline mariyu noradrinaline bandhinchakundaa nirodhistundi. grahakalanu nishkriyam cheyadam valla saadhaaranamgaa agonist motaadu-pratispandana vakrarekhala yokka garishta pratispandana yokka maandyaaniki daariteestundi mariyu pootii laeni pratyarthula maadirigaane grahaka nilva unna chota vakrarekhalo saraina maarpu sambhavistundi. pareekshalo washout dasha saadhaaranamgaa pootii laeni mariyu tirigi maarchaleni virodhi aushadhaala madhya thedaanu gurtistundi, endukante pootii laeni satruvula prabhavalu tirigi maarchabadataayi mariyu agonist yokka kaaryaacharana punaruddharinchabadutundi.
tirigi pondaleni pootii satruvulu graheeta yokka agonist mariyu virodhi madhya pootiini kooda kaligi untaaru, ayithe samayojaneeya bandham yokka raetu bhinnamgaa untundi mariyu virodhi yokka anubandham mariyu pratispandanapai aadharapadi untundi. kontamandi satruvulaku, vaaru poteegaa pravartinche pratyaekamaina kaalam undavacchu (besal saamardhyamtho sambandham lekunda), mariyu grahaka-ligand kinetics dwara nirnayinchabadina graahakamtho swechchagaa anubandham kaligi mariyu vidipovachhu. conny, tirigi maarchaleni bandham jarigina tarvaata, grahakam nishkriyam cheyabadutundi mariyu ksheenistundi. tirigi pondaleni pootii vyatiraeka aushadhaalato kriyaatmaka pareekshalalo pootii laeni satruvulu mariyu tirigi maarchaleni satruvula vishayaanikosthe, logg ekagrata-prabhavam vakrarekhalo kudi vaipuku maarpu undavacchu, conny, saadhaaranamgaa, vaalu taggudala mariyu taggina garishta rendoo pondabadataayi.