chikilsikkunnathil risapttar athiraalikal

chikilsikkunnathil resepterile histaamaininte pravartthanam thadayaan upayogikkunna marunnukalude vargeekaranamaanu chikilsikkunnathil risapttar aantagonist.
praadhamikamaayi peripheral pravarthanangalulla mayappeduthunna, echu1 resepterukalil ninnu vyathyasthamayi, ennaal avaa thalachoril thadassappettaal mayakkathinu kaaranamaakunnu, chikilsikkunnathil resepterukal praadhamikamaayi thalachoril kaanapedunnu, koodaathe hystaminergic naadi terminalukalil sthithicheyyunna inhibittari autoriseptarukalumaanu, avaa histaamain release modulate cheiyunnu. cerebral courtexile mayappeduthunna resepterukalude uthejanathiloode glutamate, asattailkolin thudangiya eksaittettari neuro traansmittarukalude dvitheeya prakaashanathinu thalachorile histaamain release kaaranamaakunnu. thathfalamaayi, mayappeduthunna mayappeduthunna aantagonist aantihistaamainil ninnu vyathyasthamayi, chikilsikkunnathil aantagonistukalkku uthejakavum nootropic efakttukalum undu, koodaathe alsheimer rogam polulla neuro degenerative avasthakalude chikilsaykkulla saadhyathayulla marunnukalaayi gaveshanam nadathunnu.
clobenpropit, abtt-239, syproxiphan, konsesin, eiii-349,821, beetaahisttin, pittolisant ennivayaanu selective chikilsikkunnathil aantaagonistukalude udaaharanagal.
charithram.
1983ll kandethiya histaamain chikilsikkunnathil risapttar risapttar parambaraagatha pharmacological reethikal upayogichu kandethiya avasaanathe resepterukalil onnaanu. kendra naadeevyavasthayil (cns) saadhaaranayaayi prakadippikkunna jii-protein-cuppled risapttar (gpcr) thirichariyaanulla shramathinte bhaagamaayi ithinte ghadana pinneedu kandethi. thalachorile farmacology valare sankeernamaanu, ithu marunninte vikasanam budhimuttaakki. thalachorile niravadhi vyathyastha pravarthanaparamaaya isophomukal nilavilundu, athaayath saidhaanthikamaayi orotta isophomine prathyekamaayi targettucheyyaan kazhiyum. ennirunnaalum, isophomukalude janithaka vyathiyaanavum oronninteyum vyathyastha pravartthanavum kaaranam athu budhimuttaayirikkum.
upayogicha signalling asse aashrayich adhdyil ligaandukale ippol agonistukal, athiraalikal allengil vipareeta agonistukal enningane tharamthirichittundu.
pravartthana samvidaanam.
adhdyil oru gpcr aanu, ithu oru presinaptic autoriseptar ennaanu visheshippikkappedunnathu, ithu histaamain purathuvidunnathu niyanthrikkukayum hettaroriseptar aayum asattailkolin, dopamine, serotonin, norpinefrine, gaba thudangiya neuro traansmittarukale niyanthrikkukayum cheiyunnu. resepterinu uyarnna ghadana pravartthanamundu, athaayath oru agonist sajeevamaakkathe signal cheyyaan kazhiyum. intra sellular kaalsyatthinte alavu swaadheenichukondu neuro traansmittarukalude prakashanam adhdyil niyanthrikkunnu. sajeevamaakumbol, ithu kaalsyatthinte ozhukkine thadayukayum ithu neuro traansmittarukalude prakashanam thadayunnathilekku nayikkukayum cheiyunnu. resepterukalude athiraalikal eee neuro traansmittarukalude samanvayathinum prakaashanatthinum kaaranamaakunnu, ithu unarvvine prothsaahippikkunnu. adhdyiles kooduthalum cnsinte hystaminergic neuronukalilaanu prakadippikkappedunnathum peripheral naadeevyavasthayude vividha mekhalakalilum ithu kaanapedunnu. thalachorinte ellah bhaagangalum kognishanumaayi bandhappettirikkunna basel ganglia, hippocampus, courtical eriyakal ennividangalile uyarnna saandrathayilaanu adhdyil kandethiyathu. alsheimer, schisophrenia, narcolepsy thudangiya rogangalude vaijnjaanika lakshanangalude pathophysiology hystaminergic systethinu oru pankundennu vivarichittundu.
vikasanam.
aadyakaala farmacophore.
adhdyil ligaandukalude vikasanathinte thudakkathil athinte ghadanayil oru imidasol valayam adangiyirikkunna agonist histaamainilaayirunnu shradha. adhdyil thammilulla gadanaaparamaaya vaividhyam parimithamaanu, innu ariyappedunna ellah adhdyil agonistukalilum oru imidasol valayam adangiyirikkunnu. imidasol adangiya samyukthangalude prashnam cytochrome pii 450 isoensaimukalude prathirodhamaayirunnu, ithu gurutharamaaya mayakkumarunnu edapedalukalkku kaaranamaayi. raktha-mastishka-thadassam marikadakkaanum avarkk budhimuttundaayirunnu. niravadhi samyukthangal pareekshichuvenkilum avaa upayogapradamaakaan kazhiyaathathra vishaamshamullavayaayirunnu.
vishaamshamullavayaayirunnu mattu resepterukalilum oof taargett function imidasol adisthaanamaakkiyulla athiraalikalil oru prashnamaayirunnu. mastishka vaikalyangalil thalachorile vaividhyamaarnna pathophysiology thalachorile athiraalikale mayakkumarunnu vikasanathinu rasakaramaakkunnu.
theoperamide.
vikasippichedutha aadyathe imidasol adisthaanamaakkiyulla ethiraaliyaaya theoperamide valare shakthavum thiranjedutthathum ennaal hepatotoxisity kaaranam oru marunnayi upayogikkaan kazhiyaathathumaan. unarvvum bodhakshaamavum mechappeduthunnathinnaani ithu aadyam roopakalppana cheythirikkunnathu. paarkkinsans rogamulla rogikalude syrcadian thaalatthinte saadhyathayulla theoperamide chikitsa aduthide nadanna oru padanatthil kaanichu.
puthiya farmacophore.
noonn-imidasol adhdyil athiraalikalilekku shradha thirikkunnu. imidasol adisthaanamaakkiyulla adhdyil athiraalikalude athe thalatthil avaa saip kudumbavumaayi edapazhakunnillennu thonnunnu, koodaathe cnsil kooduthal eluppathil ethaan kazhiyum. nirbhagyavashaal herg keey + chaanalumayulla sakthamaaya bandhanam, phospholipidosis, pii-jipi substratile prasnangal thudangiya mattu prasnangal uyarnnuvannittund. herg keey + chaanalumayulla sakthamaaya bandhanam kyudi dairkhyavardhanavinu kaaranamakum.
pittolisant.
klinikkal pareekshanangalilekku neengiya aadyathe ethiraaliyum vipareeta agonistum pitolisantaayirunnu, usl europileyum regulatory adhikaarikal amgeekaricha eaka marunnaanith. ithu chikilsikkunnathil resepterinu valare selective aanu. pitolisantinu uyarnna ooral bioavilability undu, ithu thalachorilekku eluppathil praveshikkunnu. kudalile kudalile ensaimiloode ithu vipulamaaya phastt-paas efakttukalkku vidheyamaakunnu. muzhuvan upapachayam pathayum ithuvare sthaapichittillenkilum athil kurachu saip ensimeukal ulppedunnu. narcolepsy baadhicha aalukalkk pakal samayat unarvu nilanirthaan ithu upayogapradamaanennu theliyikkappettittund. klinikkal pareekshanangalil neridendivanna paarshwafalangal dosine aashrayichirikkunnavayanna kandethi. pratheekshichathupole, chila prathikoola phalangal neuro psychiatric swabhaavamaayirunnu, avayil ettavum saadhaaranamaayath urakkamillaayma, thalavedana, uthkanda ennivayaayirunnu. pittolisant deerghakaala kyudi edavelaykku kaaranamakum, athinaal hridaya rogikalil jagrata palikkaan nirddeshikkunnu. dosukal kazhiyunnathra kuraykkunnathu prathikoola sambhavangalude apakadasaadhyatha kuraykkum.
wakics enna vyaapaaranaamathil ithu kaanapedunnu, ithu oru anatha marunnayi kanakkaakkappedunnu. 2016 march march europian kammeeshan ithu amgeekarichu. ithu 4.5 milligram, 18 milligram gulikakalil labhyamaan.
ghadana pravartthana bandham.
thalachorile ethir bandhathinu aavashyamaaya oru pothuvaaya gadanaaparamaaya paatten vivarichittundu. oru adhdyil ethiraaliykku oru dhruva grouppumaayo mattoru adisthaana grouppumaayo lipophilic mekhalayumaayo bandhippichirikkunna oru sugandha/lipophilic mekhalayumaayi bandhippichirikkunna oru adisthaana amine group undaayirikkanam.
klinikkal praadhaanyam.
adhdyil athiraalikal/vipareeta agonistukal cnsinte rogangal chikilsikkaanulla saadhyamaaya maarggam prakadippikkunnu, udaaharanathinu alsheimer rogam (edii), attanshan dephisit hyper aaktivitti syndrome (adhd), schisophrenia (eshh), vedana, narcolepsy.
narcolepsy.
vittumaaraatha urakkakkurav kondu savisheshamaaya oru urakka thakaraaraan narcolepsy. cataplexy, hypnagogic haalosineshan, sleep paralis ennivayum narcolepsy undakam. adhdyil vairudhyam cerebrospinal draavakathilekku histaamain purathuvidunnathilekku nayikkunnu, ithu unarvvu prothsaahippikkunnu. athinaal, narcolepsy chikilsikkaamenna pratheekshayil adhdyil athiraalikalekkurichu padichu. narcolepsy chikilsaykkaayi pitolisantinu amgeekaaram nalkiyittundu, mattu adhdyil athiraalikal klinikkal pareekshanangalilaan.
alshimezhs rogam (AD).
thalachorile purogamana neuro degenerative rogamaanu alsheimer rogam. parasyatthil histaamain nannayi rekhappeduthappetta punk vahikkunnu, ennirunnaalum thalachorinte vividha bhaagangalil histaamaininte vyathyastha alavukal hystaminergic neuro transmission parasya pathology thammilulla nerittulla bandham prakadippikkunnathu budhimuttaakkunnu. "inn vivo" padanangal kaanikkunnath niravadhi adhdyil athiraalikal padanavum oormmayum sugamamakkunnu ennaanu. theoperamide ചികിത്സിക്കുന്നതിൽആrine thadayukayum neuronal histaamain release vardhippikkukayum cheiyunnu, ithu mayappeduthunnaarr, echu1aarr ennivayiloodeyum mattu resepterukaliloodeyum (iii.jii. collinergic, gaba). thalachorile thalachorile valiyoru bhagam courtical, thalamocourtical neuronukalil aazhathil sthithicheyyunnathinaal parasyatthile hystaminergic neuronukalude apachayathinu adhdyil eksprashanukalumaayi bandhamilla.
attanshan dephisit hyper aaktivitti desorder (adhd).
kuttikalil ettavum kooduthal kaanapedunna oru neuro developmental disorderaanu adhd. nilavile pharmacological chikilsakalil uttejaka marunnukal adangiyirikkunnu (udha.jii. methylphenidate), uthejakamallaatha marunnukal (udha.jii. aattomoksettin), α2 agonistukal. eee marunnukal prathikoola phalangal undaakkukayum chilatharam marunnukalkk asakti undakkaan saadhyathayund. athinaal badal chikilsakal vikasippikkunnath abhikaamyamaanu. "asattailkolin, dopamine thudangiya neuro traansmittarukalude release uyarthunnathiloode shradhaykkum vaijnjaanika pravartthanatthinum sahaayikkunnathin adhdyil adhdyil athiraalikale upayogikkaanulla saadhyatha inn vivo padanangal kaanikkunnu.
schisophrenia.
schisophreniayil, mattu neuro traansmittar systengalkkoppam dopaminergic paathakalum rogathinte vikasanathil pradhana punk vahikkunnu. nilavilulla chikilsakal onnum randum thalamurayile anticycoticsine adisthaanamaakkiyullathaanu. eee marunnukal pradhaanamaayum dopamine athiraalikalaanu, avaa abhikaamyamallaatha niravadhi paarshwafalangalkku kaaranamakum. hystaminergic neuronukalum schisophreniayil oru punk vahikkunnathayi thonnunnu, koodaathe echu 3 resepterukal gabarjik neuronukalile dopamine resepterukalumaayi saha-praadeshikavalkkarikkuppadu. schisophreniayude negatteevu, cognitive lakshanagal chikilsikkunnathil chikilsikkunnathil risapttar athiraalikal upayogapradamaayekkaam, avaa athinte positteev lakshanangalude chikilsayil phalapradamallengilum. 

