nisoxetine

1970 chya dashakachya suruvatila lilly sanshodhan prayogshalanmadhye moolatah sanshleshit kelele nisoxetine heey norpenephrin (noradrinaline) chey synapsmadhye punargrahan karnyasathi eka shaktishali aanee nivadak avarodhak aahe. jaree mulat tyache antidepressant mhanoon sanshodhan kele gele asale taree sadhya manavanmadhye tyache konatehi clinical anuprayog naheet. nisoxetinecha aata vaidnyanik sanshodhanat manak nivadak norpinephrine reptech avarodhak mhanoon mothya pramanat vapar keela jaato. laththapana aanee urja santulanache sanshodhan karnyasathi yacha vapar keela gela aahe aanee kahee sthanik vedanshamak prabhav lagoo karatat.
sanshodhakanni norpenephrine transporterchya (nett) positron utsarjan tomography (paliv prani) imagingsathi nisoxetine carbon-label kelele swaroop vaparnyacha prayatna keela aahe, parantu tyat farse yash midale nahee. tathapi, asey disate qee tritium label kelele nisoxetine nisoxetine, (3etch-nisoxetine heey norpenephrine grahan sthalanna 'inn vitro' asey label karnyasathi eka upayukt radiolegand aahe, jeey nisoxetine aanee netsathi itar virodhi pratibandhit karnyas saksham aahet.
itihas.
nairashyavar upchar kartana, asey siddha kele gele qee norpenephrin sankraman vadhavu shakanare padarth, jase qee tricyclic antidepressants (tii. see. aii.), clinical nairashyachi lakshane qamee karoo shakatat. nisoxetinechi utpatti fluoxetine (prozac, ellie lilly) shodhat aadhalu shakate. 1970 chya dashakat bryan bii. molloy (eka aushadhi rasayanshastradnya) aanee robbert rathban (eka aushadhashastradnya) yanni sambhavya avasadarodhi ghatakancha shodh ghenyasathi eka sahkarya suru kele jeey ajunahi avanchhit cardiotoxicity aanee anticholinergic gunadharmanshivay tii. see. aii. chee upcharatmak kriya tikavoon thewel. histamine virodhi aushadh defenhydramine heey histamine receptorschya virodhkanvyatirikt monoamineche sevan rokhate asey aadhalun aale aanee monoamineche sevan rokhane haah nairashyachya upcharansathi eka sambhavya vapar banala. parinami, molloyne, smiggle aanee hausar yaa yaa, phenoxyphenylpropyline (pii. pii. aii.) gatachya sadasyanna defenhydramine pratirup mhanoon sanshleshit kele.
rathban prayogshaletil richard kattau yanni undaranmadhye (piham) apomorphine-prerit hypothermia ulat karnyachya kshamatesathi pii. pii. aii. ess. chya maliket navyane tayar kelelya aushadhanchi chachani kelee, hii chachani jyamadhye tii. see. aii. sakriy virodhi hote. kattaula aadhalale qee yaa maliketil eka sadasya, sadasya (nisoxetine), pihamchya ulatya prakriyet tikasaitkach shaktishali aanee prabhavi hota. serotonin (5-etch. tii.) kinwa dopaminechya aaharache shaktishali avarodhak mhanoon kaam naan karata, menduchya synaptosomesmadhye norpenephrine sevan rokhanyat nisoxetin heey decipramineitkech shaktishali asalyache aadhalun aale.
nisoxetinechi surakshitata aanee sambhavya yantraneche moolyankan karnyasathi 1976 madhye manavanmadhye purv chikitsalayin abhyas dekhil kele gele. majjatantuchya antim bhaganvar norpinephrin aanee tyramine sevan rokhanyas saksham asalelya matranmadhye, nisoxetine konatehi lakshaniy dushparinam jhaale naheet. asamanya electrocardiogram parinam dekhil disun aale naheet, jeey teey tulanene surakshit sanyug asalyache darshavtat.
tathapi, nantar, sanshodhakanni asha margancha vichar keela jyamadhye pii. pii. aii. maliketil sookshm rasayanik farak nivadakpane 5-etch. tii. grahan rokhu shakatat, jyamule akheris nisoxetinechya 4-trifluoromethyl analogue, fluxetine sanshleshan jhaale. fluoxetin yaa nivadak serotonin reaptech inhibitorchya (ess. ess. aar. aay.) vikasat adhik swarasya asalyamule nisoxetinche kadhihi aushadh mhanoon vipanan kele gele nahee.
sanshodhan.
laththapana.
anek purave asey suchavatat qee catecholaminergic signalingmadhye (norpenephrin aanee dopamaindware peshi sanvad) badal karoon, urja santulanachya niyamanat guntalelya abhijat hypothalamic pranalindware annache sevan aanee sharirachya vajanavar parinam hoil. asamanya antidepressant bupropian sarkhya antidepressantmule, bahya koshikeey dopamine aanee norpinephrin yanche sevan rokhoon vadhavanyachya tyanchya kshamatemule vajan qamee houu shakate. itar sanshodhanat serotonin aanee norpinephrine parasparsanvadavar laksh kendrit kele gele aahe, jyamule laththapana virodhi aushadhe mhanoon serotonin-norpinephrin reptech inhibitors (snris) hotat.
urja aanee sathavanukichya upalabdhatebaddal mahitee prasarit karnara paridhiy sanketancha prathamik agra mastishk sanvedak hypothalamuscha (aii. aar. etch.) arquate nucleus aahe aanee tyat done prakarchya peshi asatat jyancha urja santulanavar virodhi parinam hoto. yaa done prakarchya peshi mhanje neuropeptide vaay (aine. pii. aay.)-abhivyakt peshi, jyamule hyperphasia aanee urja sanwardhan hote aanee pro-opiomelanocourtin (pomak) peshi, jyaa hypophagea aanee vadhiv urja kharchashi sambandhit aahet. aine. pii. aay. aanee norpinephrine heey donhi mendu aanee parighatil nivadak neuronsmadhye sthanbaddh aahet. nisoxetinesarkhya norpinephrine reptech inhibitarmule aine. pii. aay. aanee norpinephrin vyakt vapar peshinchi kriyashilata qamee houn anorexia houu shakato.
dubale aanee lathth undaranmadhye, nivadak aanee ektrit norpinephrin aanee dopamineche punargrahan pratibandhamule annache sevan aanee sharirache vajan qamee hote. tarihi norpinephrin aanee dopamine (nisoxetine aanee anukrame jee. bii. aar. 12783 haah sanketik naav asalela padarth) yanche nivadak punargrahan avarodhak swatantrapane undaranchya annachya sevanavar parinam karat naheet. tathapi, jevha ekatra dile jaate, tevha ann sevan karnyas tivra pratibandh asato. heey snrisachya krutipramanech, sevan vartan niyantrit karnyasathi dopamine aanee norpinephrin yanchyatil sahakriyatmak parasparkriya darshavate. keval nisoxetinecha annachya sevanavar parinam hott nahee hii vastusthiti soochit karate qee keval norpinephrin heey aaharavar parinam karnyasathi apurate kinwa nisoxetinedware bund kelele norpinephrine punargrahan chukichya thikani karya karat aahe. nisoxetinechya ulat, tyache sulfur analogue thynesoxetine undiranmadhil annache sevan qamee karate aanee laththapana aanee khanyachya vikaransathi adhik aashadayak upchar aahe.
vedanshamak prabhav.
soodiyam vahinyanna adavane haah sthanik bhool deuun sodanyacha eka aavashyak upkram aahe. asha prakare, sthanik bhool deuun aat ghusun tvachevar vednadayak vedna, paridhiy majjatantu avarodhak, tasech pathicha kanaa/epidural bhool deuun sodane tayar karata yete. nisoxetinechya soodiyam vahini avarodhit karnyachya prabhavamule, tyacha sthanik bhooldayak prabhav dekhil asoo shakato. nicotinic acetylcholine receptorschya karyavar velee parinamandware, nisoxetine heey hippocampal norpinephrine nikotin-prerit vadhis, matrevar avalambun asalelya swarupat dadapanyat saksham aahe. heey undaranchya varchya grivechya gangliamadhye tetrodotoxin-sulabh sanvedanshil aateel soodiyam pravah rokhanyat dekhil saksham aahe.
nisoxetine sthanik (tvachecha) parinam karate parantu pranaligat vedanshamak nahee. lidocane yaa samanya bhool denyachya tulanet, nisoxetine adhik shaktishali (chaar patinni) asate aanee tvachechya bhool denyachya dishene aushadhanchi dirghkal chalanari krutee darshavate. aine. emm. dii. aii. receptors yaa sthanik bhooldayak prabhavat sahbhagi nasatat. tathapi, nisoxetinemule majjatantu kinwa tvachekhalil uutinmadhye vishaktata yeu shakate qee nahee heey aspasht aahe, jyachi bhavishyat adyap tapasani karane aavashyak aahe.
dusarikade.
norpinephrine punargrahan sthalasathi purvi upalabdh asalelya radiolegandschya kamataratemule, sanshodhakanna norpinephrine punargrahan sthalanche mojmap karnyasathi eka changla legand shodhane aavashyak hote. yaa kamataratancha arth assa dekhil hota qee mendutil norpinephrine grahan sthalancha abhyas 5-etch. tii. grahan sthalanpeksha qamee keela gela hota. norpinephrine grahan sthalansathi purvichya radiolegandsmadhye, hoto-decipramine 3etch-decipramine aanee hoto-magindol 3etch-magindol, norpinephrine sthalansathi vishisht aanee nivadak bandhan gunadharm navhate.
dusarikade, dusarikade 3etch-nisoxetin. aay. ess.) haah norpinephrine sevanasathi eka shaktishali aanee nivadak avarodhak aahe aanee aata norpinephrin transportercha nivadak chinhak mhanoon vaparla jaato. hoto-nis vaparoon kelele bahutek abhyas undaranchya namunyat kele jaatat aanee barechase manavanmadhye kele gele naheet. hoto-nischa vapar norpinephrine grahanshi sambandhit sharirik sthalancha nakasha tayar karnyasathi parimanatmak autoridiography (qr) chya tantradvare keela jaau shakato, jithe jithe bandhanicha namuna norpinephrin sakriyatechya namunyashi susangat aahe. jakhamechya abhyasatoon hoto-nisacha precineptic norpinephrine terminalshee asalela sambandh dekhil siddha hoto.
hoto -nees uchch aatmiyata (keey. dii. = 0.7 nm) aanee undaranchya mendumadhil norpinephrine sevanashi sambandhit asalelya sthalanchya eksandh loksankhyeshi nivadaktesah bandhate. sodiyamche praman vadhalyane vishisht 3h-nis bandhan vadhate aanee sodiyamchya anupasthitit 3h-nis bandhan kvachitach shodhata yete. 3h-nis chey bandhan soodiyam-aadharit aahe kaaran norpinephrine neuronal grahanasathi soodiyam aayan aavashyak aahet. heey bandhan dekhil ushnateshi sanvedanshil asate, jethe under cerebral cortical membrain garam kelyane vishisht bandhananche praman qamee hote. nisoxetine (qee = 0.7 + 0.02 nm), tasech norpenephrin grahan sthalanshi (dii. emm. aay., mazz, maprotylene) uchch sambandh asaleli itar sanyuge, hoto-aine. aay. ess. chey undaranchya cortical patalanshi bandhanare shaktishali avarodhak mhanoon karya karatat.
manavanmadhye, hoto-nischa vapar locus corulius (elsie) madheel grahansthale mojanyasathi keela jaato. norpinephrine akshatantuncha srot asalelya ell. see. varr, manavanmadhye vruddhatvachya velee velee bhagat peshi nasht honyachya ahavalanmule sanshodhanat laksh kendrit kele gele aahe. hoto-nische bandhan qamee hone heey ell. see. peshinche nuksan darshavate.
paliv pranyancha vapar karoon nett imaging.
positron utsarjan tomography (paliv prani) vaparoon sanshodhak norpinephrine transporter (nivval) pranalichi pratima kadhanyacha prayatna karat aahet. yaa paddhatisathi vaparlya vaparlya sambhavya legandsmadhye uchch aakarshan aanee nivad, uchch mendu pravesh, yogya lipophilicity, plazmamadhye vajvi sthirata tasech uchch plazma mukt ansh asane aavashyak aahe. 11 see-label kelele nisoxetine, hakah aanee kilborne yanni sanshleshit kelele, eka sambhavya umedvar hote jyacha sambhavya paliv pranyancha shodhak mhanoon vapar kelyabaddal tapas keela gela. tathapi, vivomadhye, 11 see-label kelele nisoxetin heey anirdisht bandhan darshavate, tyamule paliv pranyansathi sambhavya legand mhanoon tyachi parinamkarakta maryadit karate.
aushadhashastriy gunadharm.
nisoxetin haah norpinephrine sevanache eka shaktishali aanee nivadak avarodhak aahe, jithe too serotoninchya tulanet norpinephrine sevan rokhanyat sumare 1000 putt adhik shaktishali aahe. dopamainpeksha norpinephrine sevan rokhanyat teey 400 putt adhik shaktishali aahe. nisoxetinechya aar-aaysomarmadhye netsathichya tyachya ess-aaysomarpeksha 20 putt jaast aatmiyata asate. neurotransmitter receptors nisoxetinecha farsa sambandh nasato kinwa nasato. nisoxetinesathi nett qee samanyatah 0.8 nm asalyache manya kele jaate.
svayamsevkansathi nisoxetin denyat aale, asha purv chikitsalayin abhyasat, ekach matrenantar sarasari plasmache praman 0.028 microgram/miilii asalyache aadhalun aale aanee pandharavya matrenantar 0.049 microgram/miilii hote. nisoxetinche bandhan manvi placental netmadhye santrupt aahe, vishisht bandhan moolye keey. dii. sathee 13.8 + 0.40 nm aanee bii. emm. aii. ex. soodiyam aanee chloridesathi prathin 5.1 + 0.1 pii. emm. oo. ell./mii. gra. asalyane nisoxetinche bandhan tyachya legandsathi bandhansthalache aakarshan vadhavun vadhate, jithe chlorideche praman qamee hott asatana keey. dii. moolye vadhatat. bii. emm. aii. ex. prabhavit hott nahee.
undaranmadhil cerebral cortical homogenatevar 3h-nis chee kriya 0.80 + 0.11 nm chee kd aanee + 12 fmol/mg prathinanchi bmax darshavate. bandhanichi ghanata samanyatah menduchya asha bhaganshi sambandhit asate, jethe norpinephrinechi patali disun yete, jethe sarvat jaast vishisht 3 etch-aine. aay. ess. bandhani hii menduchya tantumadhye (ell. see.) aanee thalamusmadhye asate. vishisht 3h-nis bandhan soodiyam catayanvar avalambun asate, jethe sodiyamche praman vadhalyamule vishisht aanee ekoon bandhan vadhavale jaate (tejani-butt aanee itar.1990). heey bandhan ekach vargatil sthalanshi uchch aakarshanasah ghadate, jyat norpinephrin grahansthalachi samaan aushadhiy vaishishtye aahet.
norpenephrin grahan sthalanche nisoxetine aanee itar avarodhak hoto-nische bandhan rokhanyat saksham aahet. jevha undaranna nisoxetine antahshira injection dile jaate aanee aanee bandhan mojale jaate, tevha 1 microne meetarparyantchya sandratesathi nisoxetinechi qee 0.8 + 0.1 nm asalyache nondavale jaate.
pratikool parinam.
dopamine aanee/kinwa itar serotonin reptech inhibitors norpinephrin, bahutekda manahsthiti vikaranchya upcharanmadhye vihit kele jaatat aanee samanyatah changle sahan kele jaatat.
1970 chya dashakat nisoxetinecha vapar vapar manavanvar purv chikitsalayin abhyas karnyat aale aanee aushadhachya dushparinamanchi tapasani karnyat aalee. 1 mii. gra. teey 50 mii. gra. paryantchya matranmule raktaranjit chachanya, niyamit rakt rasayanshastra kinwa gothan mapdandanmadhye aadhar reshechya mulyanmadhye konatahi badal hott nahee. mothya matremule kahee dushparinam hotat, parantu konatyahi matret konatehi electrocardiographic badal disun yet naheet. nisoxetin prapt kartana manavanmadhye tyraminechya matresah injection dilyane prashasit nisoxetinchya vadhiv kalavadhisah tyraminela pratisad qamee hoto. nisoxetinechya prashasanacha aanakhi eka parinam mhanje jyanna placebo midato tyanchyapramanech raktadab pratisad nirman karnyasathi lokanna norpenephrinechya khoopach qamee matra aavashyak asatat. asatat shabdant, nisoxetine dilyanantar vishay norpinephrinaprati vadhaleli sanvedansheelata darshavtat. purv chikitsalayin chachanicha nishkarsh assa aahe qee chachani kelelya matranmadhye heey aushadh manavanmadhye vaparnyasathi surakshit asalyache disate.
rasayanik gunadharm.
nisoxetine heey done isomers asalele resemic sanyug aahe.
tricyclic (teen-ring) sanrachana anek vegvegalya aushadhanmadhye aadhalu shakatat aanee aushadhi rasayanshastradnyansathi samanya carbon kinwa hetero (carbon nasalela) anoola jodalelya done phenyl ringschya sanrachanatmak halchalinvar nirbandh ghalanyachi parvanagi detat. paryay kinwa ring lavchikta yasarkhe lahan aanvik badal, aushadhachya aushadhashastriy aanee bhautik rasayanik gunadharmanmadhye badal ghadavun aanoo shakatat. phenoxyphenylpropymine krutichi yantrana ringchya paryayacha prakar aanee sthitichya mahattvapoorn bhoomikedware spasht kelee jaau shakate. adlabadal naan kelela renu haah eka kamkuvat ess. ess. aar. aay. aahe. eka sanyug, jeey norpinephrine punargrahan rokhanyasathi atyant shaktishali aanee nivadak aahe, heey phenoxy ringmadhye 2-paryayanmule udbhavate.

