Mianserin, insonlar orasida Tolvon nomli brend nomi ostida sotiladigan, asosan yevropa va dunyoning boshqa joylarida depressiyaga qarshi kurashishda ishlatiladigan atipik antidepresantdir[1]. Bu tetrasiklik antidepresant (TeCA) hisoblanadi. Mianserin mirtazapin nomli dori bilan kimyoviy va tarkibi hamda taʼsiri jihatidan yaqin, garchi ikkita dori oʻrtasida sezilarli farq boʻlsa ham[2].

Tibbiy maqsadlarda foydalanish

tahrir

Mianserin yuqori dozalarda (kuniga 30-90mg) katta depressiv kasalliklarni davolash uchun ishlatiladi[1].

Bundan tashqari, uyqusizlikni davolash uchun kamroq dozalarda (kuniga 10 mg) ishlatilishi mumkin[3][4].

Qoʻllash mumkin boʻlmagan holatlar

tahrir

Bu tibbiy yordam 18 yoshdan kichik insonlarga klinik ehtiyojlarga asoslangan va qatʼiy tibbiy nazorat ostida boʻlmagan holda berilmasligi kerak, chunki bu oʻz joniga qasd qilishga urinishlar va oʻz joniga qasd qilish fikrlash xavfini oshirishi va tajovuzkorlikni oshirishi mumkin[1].

Hayvon modellaridan homilaga zarar yetkazishi mumkinligi haqida hech qanday dalillar yoʻq boʻlsa-da, homilador ayollar uchun uni qabul qilish xavfsizligini koʻrsatadigan maʼlumotlar yoʻq[1].

Ogʻir jigar kasalliklariga chalingan bemorlar mianserinni qabul qilmasligi kerak va epilepsiya yoki tutilish(tutqanoq) xavfi boʻlgan odamlar bundan ehtiyotkorlik bilan foydalanishlari kerak, chunki bu tutilish xavfini pasaytirishi mumkin. Agar klinik qarorga asoslangan boʻlsa, oddiy ehtiyot choralarini koʻrish va mianserinning dozalari va har qanday parallel terapiyani koʻrib chiqish va kerak boʻlganda tuzatish kerak[1].

Nojoʻya taʼsirlari

tahrir

Juda keng tarqalgan (tasodif > 10%) salbiy taʼsirlar: qoʻriq, ogʻiz qurishi va davolash boshida uxlash[5][1].

Oddiy (1% < hodisa ≤ 10%) salbiy taʻsirlar:parvarishlash terapiyasi paytida uyquchanlik, tremor, bosh ogʻrigʻi, bosh aylanishi, vertigo va zaiflik kiradi[5].

Kamdan-kam (0,1% < hodisa ≤ 1%) salbiy taʻsirlar: inson vazninig ortishi[5].

Tez toʻxtatib qoʻyish

tahrir

Mianserinni toʻsatdan yoki tezda toʻxtatish ogʻir kasalliklarni keltirib chiqarishi mumkin, uning oqibatlari-depressiya, tashvishlanish, vahima hujumlari[6], ishtahaning pasayishi yoki anoreksiya, uyqusizlik, diareya, koʻngil aynishi va qusish va grippga oʻxshash alomatlar, masalan, barcha allergiya yoki qichishish va boshqalar.

Dozani oshirib yuborish

tahrir

Mianserinning haddan tashqari koʻp istemol qilish sedasyon, koma, gipotenziya yoki gipertenziya, taxikardiya va QT oraligʻini uzaytirishi mumkin[7].

Oʻzaro taʼsirlari

tahrir

Mianserin birgalikda qoʻllanganda spirtli ichimliklar, anksiyolitiklar, gipnozlar yoki antipsikotiklar kabi dorilarning sedativ taʼsirini kuchaytirishi mumkin. Antiepileptik dorilarning samaradorligini pasaytirishi mumkin.

Karbamazepin va Fenobarbital mianserinni tezroq metabolizatsiya qilishini va uning taʼsirini kamaytirishi mumkin. Agar odamlar diazoxid, hidralazina yoki nitroprusid bilan birga mianserinni qabul qilishsa, qon bosimining xavfi xavfli darajada pasayishi kuzatiladi. Mianserin antihistamin va anti-muskariniklarni kuchaytirishi mumkin. Mianserinni apraklonidin, brimonidin, sibutramin yoki artemeter va lumefantrin kombinatsiya dorilari bilan birga qabul qilish kerak emas[1].

Farmakologiyada

tahrir

Farmakodinamikasi

tahrir
Mianserin[8]
Site Ki (nM) Species Ref Human [9]
71 Human [9]
9,400 Human [9]
5-HT<sub id="mwog">1A</sub> 400-2,600 Human [10][11]
5-HT<sub id="mwrQ">1B</sub> ≥2,800 Rat [12]
5-HT<sub id="mwtg">1D</sub> 220-400 Human [13][14]
5-HT<sub id="mwwQ">1E</sub> ND ND ND
5-HT<sub id="mwyw">1F</sub> 13 Human [10]
5-HT<sub id="mw1A">2A</sub> 1.6-55 Human [15][16]
5-HT<sub id="mw3w">2B</sub> 1.6-20 Human [17][18]
5-HT<sub id="mw6g">2C</sub> 0.63-6.5 Human [15][19]
5-HT<sub id="mw9Q">3</sub> 5.8-300 Rodent [20][11]
5-HT<sub id="mwAQA">4</sub> ND ND ND
5-HT<sub id="mwAQo">5A</sub> ND ND ND
5-HT<sub id="mwARQ">6</sub> 55-81 Human [21][22]
5-HT<sub id="mwAR8">7</sub> 48-56 Human [23][24][25]
α<sub id="mwASw">1</sub> 34 Human [26]
α<sub id="mwATU">2</sub> 73 Human [26]
  α<sub id="mwAUA">2A</sub> 4.8 Human [23]
  α<sub id="mwAUs">2B</sub> 27 Human [27]
  α<sub id="mwAVY">2C</sub> 3.8 Human [23]
D<sub id="mwAV8">1</sub> 426-1,420 Human [11][23]
D<sub id="mwAWo">2</sub> 2,100-2,700 Human [26][28]
D<sub id="mwAXU">3</sub> 2,840 Human [26]
D<sub id="mwAX4">4</sub> ND ND ND
D<sub id="mwAYg">5</sub> ND ND ND
H<sub id="mwAZI">1</sub> 0.30-1.7 Human [29][26][23]
H<sub id="mwAZ8">2</sub> 437 Human [30]
H<sub id="mwAag">3</sub> 95,500 Human [30]
H<sub id="mwAbE">4</sub> >100,000 Human [30][31]
820 Human [26]
21,000 Human [32]
30,200 Human [32] Human [32]
Values are Ki (nM), unless otherwise noted. The smaller the value, the more strongly the drug binds to the site.

Mianserin oʻz taʼsirini histamin va serotonin retseptorlarining antagonizmi va norepinefrin vositalarini qayta qabul qilinishini toʻxtatish orqali amalga oshirishi koʻrildi. Xususan, u histamin H1 retseptorining koʻp yoki barcha joylarida anthistamin:WikiLink" title="Inverse agonist">akronist /invers agonist, serotonin 5-HT<sub id="mwAe0">1D</sub>, 5-HT<sub id="mwAe8">1F</sub>, 5-HT2C" id="mwAfI" rel="mw: WikiLink" title="5-HT2B">5-HT2B" id="mwAfA" rel="mw: WikiLink" title="5-HT2A">5-HT2A, 5-HT 2B, 5-HT<sub id="mwAfc">3</sub> , 5-HT<sub id="mwAfk">6</sub> va 5-HT7 retseptorlari, adrenergik α1-va α2-adrenergik retseptorlari va shuningdek, norepinefrin qayta qabul qilish inhibitori hisoblanadi[33][34]. H1 retseptorlari yuqori darajaga ega boʻlgan agonist sifatida mianserin kuchli antihistamin taʼsirlariga ega (masalan, sedatsiya). Aksincha, u muskarinik asetilkolin retseptorlariga kam yaqinlik qiladi va shuning uchun anticholinergik xususiyatlarga ega emas[26]. MI kichik afinatli, ammo k-oploid retseptorining (Ki = 1.7 μM; EC<sub id="mwAhM">50</sub> = 0.53 μM) qismli agonisti boʻlishi aniqlandi[32][35].

H 1 va, ehtimol, a 1 -adrenergik retseptorlarini qayta ishlash sedativ taʼsirga ega [5], shuningdek, 5-HT 2A va a 1 -adrenergik retseptorlari antagonizmi hujayra ichidagi fosfolipaza C (PLC) faollashishini nazorat qiladi, bu jarayon keng tarqalgan hisoblanadi. Antidepressantlar bir necha turli sinflar uchun maqsad boʻlishi mumkin[36]. Asosan, nazoratlovchi avtoretseptorlar va heteroreseptorlar vazifasini bajaradigan somatodendritik va presinaptik a 2 -adrenergik retseptorlarini antagonizatsiya qilish orqali mianserin miya va tananing turli sohalarida norepinefrin, dopamin, serotonin va asetilkolin chiqarilishini nazorat qiladi.

Mirtazapin vositasi bilan bir qatorda, nisbatan kamroq darajada boʻlsa ham, mianserin baʼzan noradrenerjik va oʻziga xos serotonerjik antidepressant (NaSSA) sifatida tavsiflangan[37]. Biroq, ushbu belgilarni qoʻllab-quvvatlovchi haqiqiy dalillar hali oʻz tasdiqini topmagan[38].

Farmakokinetik

tahrir

Mianserinning tabiatda biologik mavjudligi 20% dan 30% gacha boʻladi[39]. Uning plazmadagi protein bogʻlanish miqdori 95% ni tashkil qiladi. MiaN N" data-linkid="568" href="./Liver" id="mwAkM" rel="mw:WikiLink" title="Liver">jigar CYP2D6 ferment tomonidan N-oksidatsiya va N-demetilatsiya orqali metabolizatsiya qilinadi. Uning eliminatsiyasi 21 soatdan 61 soatgacha boʻladi. Bu dori tanadan siydik orqali 4% dan 7% gacha va najas orqali 14% dan 28% gacha chiqarib tashlanadi[39].

 
- MianS.

Mianserin — tetratsiklik piperazinoazepin hisoblanadi. Mirtazapin bir xil organik kimyogarlar jamoasi tomonidan ishlab chiqilgan va halqalardan birida azot atomining qoʻshilishi bilan hosil boʻlgan[40][41]. (S)-(+) -Mianserin oʻzining enantiomeridan (R)-(-)-mianserindan taxminan 200-300 marta faolroq; demak, mianserinning faolligi (S)-(+) izomerida yotadi. </link>[ iqtibos kerak ]

Tarixi

tahrir

Bu dori Organon International tomonidan ishlab chiqilgan, ammo kashf etilmagan; birinchi patentlar 1967-yilda Gollandiyada berilgan va 1979-yilda Fransiyada Athymil nomli brend ostida ishga tushirilgan va shundan soʻng Buyuk Britaniyada Norval nomidan ishga tushirilgan. AQShda klinik sinovlar oʻtkazganda tadqiqotchilar firibgarlik maʼlumotlarini taqdim etishdi va bu vosita AQShda hech qachon tasdiqlanmagan[42]:21[43]:318.

Mianserin Buyuk Britaniyada birinchi antidepressivlardan biri boʻlib, bu tritsiklik antidepressivlarga qaraganda xavfi nisbatan kamroq; lekin kamroq boʻlsa ham 2012-yildan boshlab Buyuk Britaniyada bu vosita qoʻllamishi bekor qilingan[44].

Jamiyat va madaniyatdagi oʻrni

tahrir
 
Mianserin.

Umumiy nomlari

tahrir

Mianserin-bu preparatning ingliz va nemischa umumiy nomi, mianserin gidroxloridi esa uning USAN Tooltip nomi. Uning frantsuz tilidagi umumiy nomi va DCF-miansérine, Ispan va Italyan tillarida DCIT-mianserina, lotincha esa-mianserinum [45][46][47][48].

Mashhur nomlari

tahrir

Mianserin mahsuloti koʻplab mamlakatlarda asosan Tolvon nomli brend ostida sotiladi. Bu vosita shuningdek, butun dunyoda Athymil, Bonserin, Bolividon, Deprivon, Lantanon, Lerivon, Lumin, Miansan, Serelan, Tetramid va Tolvin kabi turli xil brend nomlari ostida mavjud[46][48][45].

Foydalanishi

tahrir

Mianserin AQShda foydalanishga ruxsat berilmagan, lekin Buyuk Britaniyada va boshqa Yevropa mamlakatlarida foydalanishga ruxsat berilgan[49][50]. 1996-yil may oyida mianserin generik dori TGA Terapeutik tovarlar maʼmuriyati tomonidan maʼqullandi va Avstraliyada sotuvga ruxsat berildi[51].

Tadqiqoti

tahrir

Psixologik sinovlarda shizofreniyaga chalingan odamlarga yordam berish uchun mianserindan foydalanish oʻrganilgan; ammo natija yaxshi boʻlmagan[52][53].

Manbalar

tahrir

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