Lorcaserin

I-CMOAPI inezinhlobonhlobo zemikhiqizo eluhlaza ye-lorcaserin, futhi inesistimu yokuphathwa kwekhwalithi ephelele .Kwadlula isitifiketi se-GMP kanye ne-DMF.

Ibonisa 4-6 yemiphumela engu-6

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Yini iLorcaserin?

I-Lorcaserin (i-Belviq) i-ejenti yokulwa nokukhuluphala. Uma ulungele ukuxukuza isisindo somzimba esengeziwe ngaphandle kokukhathazeka ngokuzivocavoca okuyisidina, nakhu okufanele ukwazi ngaphambi kokuthenga isidakamizwa se-serotonergic.
ILorcaserin hydrochloride yathuthukiswa yi-Arena Pharmaceuticals. Eminyakeni edlule, ibisetshenziswa njengokwelashwa kwesikhathi eside ukukhuluphala. Isengezo sinciphisa inkanuko ngokwandisa ukusutha. Ngaphandle kwalokho, ukusebenza kahle kwe-lorcaserin akudingi ukuthi ulandele izindlela ezithile zokudla noma izindlela zokuvivinya umzimba.
Kusukela saqala ukusebenza, lesi sidakamizwa senziwe izivivinyo eziningi zangaphambi kokuhlinzwa kanye nezifundo zabantu ukuthola ukusebenza kwaso nokubekezelela ekwelapheni ukukhuluphala. Ku-2012, i-FDA ivume i-lorcaserin (Belviq) yokusetshenziswa kokwelapha kepha ngaphansi kwezinyathelo ezinzima. Isibonelo, umuthi kadokotela-utholakale kuphela kubantu abakhuluphele nabakhuluphele ngokweqile abane-comorbidities ehlobene nesisindo njenge-hypertension, isifo sikashukela kanye ne-dyslipidemia.
Kunamagama amabili aziwayo e-lorcaserin, okungukuthi, iBelviq neBelviq XR. Zombili zicishe zifane, zine-lorcaserin hydrochloride njengesithako esisebenzayo.
Ama-capsule we-Belviq mancane kancane, futhi ububanzi bomthamo buhlukaniswa kabili ngosuku. Ngokuphambene ne-Belviq XR capsules mikhulu kakhulu. Leli gama lomkhiqizo we-lorcaserin linamaphilisi wokukhishwa okwandisiwe we-orange okufanele athathwe kanye ngosuku.


Abashayeli beLorcaserin kanye neLorcaserin

I-Racemic Chlorocaserin Hydrochloride

Le nhlanganisela ibizwa kakhulu nge-lorcaserin hydrochloride. Kodwa-ke, igama layo lesayensi yi-8-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine Hydrochloride (CAS: 1431697-94-7).
I-Racemic Chlorocaserin Hydrochloride powder itholakala ngokuxuba i-dextrorotatory chlorocaserin hydrochloride ne-lev-rotor chlorocaserin hydrochloride. I-lorcaserin intermediate isetshenziselwa ukutadisha nokulungiselela umuthi osebenzayo wokwehlisa isisindo.

I-Dextrorotatory Chlorocaserin Hydrochloride

Le nto yaziwa ngamakhemikhali njenge (R) -8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (i-CAS no: 846589-98-8). Kodwa-ke, ngokwemibandela ye-layman, yi (R) lorcaserin hydrochloride.
Lokhu okuphakathi kwe-lorcaserin kuyinto eluhlaza ehlaziywayo yokutadisha izakhiwo zemithi yemithi yokwehlisa isisindo. Ezifundweni ezandulela ukwelashwa ngamagundane, i-compound ikhombisa imiphumela ye-anorectic. Ngaphandle kwalokho, kunciphisa nokutholwa kwama-analgesics nezidakamizwa ezifana ne-caffeine, i-amphetamine, kanye nezidakamizwa ezihlobene nayo.

I-Green Casserole Esandleni Sokudla

Ngokwesayensi, lokhu (R) -8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzazepine nge-CAS no. 616202-92-7.
I-casserole eluhlaza ngesandla sokudla iyatholakala ngezizathu zokuhlaziya nezokutadisha. Le nto i-agonistic ekhethiwe kuma-receptors we-5-HT2C, ngakho-ke, ilusizo ocwaningweni lwezidakamizwa ezinganciphisi ukudla.

I-Dextrorotatory Chlorocaserin Hydrochloride Hemihydrate

Le nhlanganisela yaziwa ngenye indlela njenge-lorcaserin hydrochloride hemihydrate. Ubunikazi bayo besayensi ngu (R) -8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride hemihydrate (CAS: 856681-05-5).
I-Dextrorotatory Chlorocaserin Hydrochloride yinto eluhlaza yokwenziwa kwe-lorcaserin.

I-Racemic Chlorocaserin Isisekelo Samahhala

Igama layo lamakhemikhali ngu-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-benzazepine (i-CAS no: 616201-80-0).
I-Racemic Chlorocaserin Free Base ingumkhiqizo wezinga lemithi ongasetshenziswa ocwaningweni nasekuhlaziyweni kwesayensi.

I-Green Card Serin Ephakathi

Igama layo lesayensi ngu-1 - [[2- (4-Chlorophenyl) ethyl] amino] -2-chloropropane hydrochloride (CAS no: 953789-37-2). IGreen Card Serin nayo iphakathi nendawo ekulungiselweni kwesengezo se-lorcaserin.
Kufanele wazi ukuthi zonke lezi zixhumanisi ze-lorcaserin zenzelwe izinhloso zocwaningo kuphela. Amakhemikhali awakulungele ukusetshenziswa komuntu noma kwesilwane.


Usebenza kanjani uLorcaserin?

I-Lorcaserin (i-Belviq) ihlose i-Central Nervous System ngokuxhumana nama-receptors athile we-hypothalamic. Isebenza ngokwenza kusebenze i-serotonin 2C (5-HT2C) kuma-pro-opiomelanocortin neurons. Le ngxenye yobuchopho inesandla ekudleni nasekwenzeni imikhuba yokudla. Yize kukhona amanye ama-receptor subtypes afana ne-5-HT2A ne-5-HT2B, lesi sidakamizwa sinokuhlangana okuphezulu kwe-5-HT2C.
Isengezo sokulahleka kwesisindo seLorcaserin senza kusebenze ama-5-HT2C receptors, yingakho, kukhuthaza ukubonakaliswa kwamahomoni e-alpha-MSH. I-Alpha-MSH isebenza kuma-melanocortin-4-receptors, athumela amasiginali ebuchosheni ukuthi usuthi.
Impahla ye-agonistic ye-lorcaserin ene-5-HT2C receptor inyusa ukusutha, ngakho-ke, ukunciphisa ukudla kanye nokusheshisa ukwehla kwesisindo. Ngokusho kweminye imibono yesayensi, lesi sidakamizwa se-serotonergic sihlehlisa amazinga e-leptin, i-hormone edlala indima ekwehliseni isisindo. Ukuhlanganiswa kokusebenzisa lesi sithasiselo njenge-ejenti yokulwa nokukhuluphala ukuthi akususi isifo senhliziyo se-valvular. Isizathu ukuthi kuncane kakhulu kuma-receptors we-5-HT2B.


Izinzuzo zeLorcaserin nemiphumela emibi

Izinzuzo

Ukuthatha i-lorcaserin hydrochloride kwandisa umuzwa wokusutha. Kuyasiza ngezinkinga zokudla, njengokujwayelekile kubantu abadla imizwa nokuzitika ngokweqile. Ngokwezivivinyo zemitholampilo eziphumelelayo, umuntu angalahlekelwa okungenani i-5% yesisindo somzimba wabo emavikini e-12.
Yize kungavamile, ukulahlekelwa ngaphansi kwesisindo sakho esingu-5% ngenkathi uku-lorcaserin kusho ukuthi awusoze wafeza noma yimuphi umphumela onengqondo ngisho nangokwelashwa kwesikhathi eside. Kuleli qophelo, abacwaningi bancoma ukuthi uyeke ukuphatha ukwengezwa kwesisindo.
Ukusebenzisa le ejenti ye-serotonergic ngokungangabazeki kuzodala inqubo yokushisa amafutha. Kodwa-ke, kufanele ufake imisebenzi ethile yomzimba ngenkathi unamathela ekudleni okunekhalori eliphansi. Ngaphandle kwalokho, ukusebenza ngempumelelo kwe-lorcaserin ekulawuleni isisindo ekulawuleni okuqhubekayo. Ukuyekisa umthamo kungathikameza imiphumela.
Ngaphandle kokuphathwa kwesisindo, i-lorcaserin nayo isebenza ngokushayela phansi ukusebenza ngokweqile kwe-dopamine ekuphenduleni izidakamizwa ezithile ezifana ne-caffeine, i-morphine, i-codeine, noma i-amphetamines. Imiphumela ye-agonistic yesengezo kuma-serotonin receptors iyenza ikulungele ukuphatha ukuphazamiseka kwengqondo.
Ngokusho kososayensi, i-lorcaserin nayo inganciphisa izimpawu ze-schizophrenia ngoba inciphisa ukukhishwa kwe-dopamine.

Okuqhamuka uma udla imishanguzo
  • Ukuphathwa yikhanda
  • isiyezi
  • Ukukhathala
  • I-nausea
  • ukukhathazeka
  • Ubuhlungu emuva noma imisipha
  • ukuqunjelwa
  • Ukuchama kaningi futhi okunzima
  • Ukulala
  • Umlomo omile
  • Umbono ushintsho njengobumnyama
  • Isikhukhula
  • Amehlo amile

Ngaphezu kwengxenye yezimpawu ezingezinhle ze-lorcaserin HCl kungenxa yokweqisa. Ungadlula imiphumela emibi ye-lorcaserin ngokunamathela kuzinyathelo zokuqapha izidakamizwa. Isibonelo, akufanele weqe ibanga lomthamo lansuku zonke. Uma kwenzeka ukweqisa ngokweqile, qiniseka ukuthi ufuna iseluleko sezokwelapha. Okunye ukuphendula okufanele kubhekwe kubalwa ukusangana, ukushintsha kwemizwelo, ubuhlungu besisu, ukushaya kwenhliziyo okungajwayelekile, ne-hysteria.

Ukuqapha:

Ngaphambi kokuphatha ukwengeza kwe-lorcaserin HCl, udinga ukucubungula ukuphikisana okulandelayo nokuqapha izidakamizwa;

  • Abanye abasebenzisi bangase babe ne-allergen kwizithako ze-lorcaserin
  • Abesifazane abakhulelwe nabomama abancelisayo akufanele banikeze i-lorcaserin ngoba ingathinta ingane
  • Isengezo singasebenzisana nemithi ethile kadokotela futhi engabhaliswanga futhi siphazamise izakhiwo zazo zemithi
  • Imithi yokwehlisa isisindo yeLorcaserin iphikisana neziguli ezisengozini yomdlavuza noma kulabo asebevele benesifo

Ubani Ongasebenzisa I-Lorcaserin?

I-Lorcaserin iyasiza ekwelapheni ukukhuluphala. Ngokomthetho we-FDA, lo muthi we-serotonergic ulungele kuphela abantu abakhuluphele ngokweqile abane-BMI engaphezu kuka-27kg / m2 nabantu abadala abakhuluphele abane-BMI enkulu kuno-30kg / m2. Kodwa-ke, incwadi kadokotela isebenza kuphela ezigulini ezinezimo ezihlobene nesisindo njenge-dyslipidemia, umfutho wegazi ophakeme, izifo zenhliziyo nemithambo yegazi.
Iziguli zabantu abadala kuphela ezingenza i-lorcaserin ithenge ukuphathwa kwesisindo okungapheli. Ukuphenya ngokuhlolwa komtholampilo ngomuthi kuqinisekisa ukwedlula izifundo zabantu ezazingaphezu kweminyaka eyi-18. Ngaphezu kwalokho, ukuphepha nokusebenza kwayo ezigulini ezingaphansi kweminyaka eyi-18 akuqinisekisiwe.
Yize noma yimuphi umuntu okhuluphele noma okhuluphele ngokweqile angasebenzisa i-lorcaserin yokunciphisa isisindo, kukhona okunye ukuphikisana emaqenjini ambalwa. Isibonelo, abesifazane abakhulelwe abaziwa. Ngaphandle kwalokho, akucaci ukuthi umuthi uyadlula yini ebisini lwebele, yingakho omama abancelisayo abakhishwa ekuthatheni.


Uyini umehluko phakathi kweLorcaserin, iCetilistat, ne-Orlistat?

Lorcaserin

I-Lorcaserin HCl iyisifiso sokunciphisa ukudla ngenkathi i-orlistat ne-cetilistat ibamba i-hydrolysis ye-triglycerides ibe ngama-fatty acids. Isengezo siqonde esifundeni se-hypothalamic sobuchopho esilawula isifiso sokudla nokugcwala. Ukuthatha i-lorcaserin kuzoqala ukusutha futhi kukhombise umzimba ukuthi ugcwele kungakhathalekile inani elincane oselidlile. Ngakho-ke, ukwehla kwesisindo kuyangena ngenxa yokwehliswa kokudla kanye nokuphazamiseka kokudla.
Nge-lorcaserin, isiguli esikhuluphele singalahlekelwa ngaphezu kwe-5% yesisindo sokuqala somzimba kanye nokwehliswa kosayizi okhalweni cishe we-3cm. Imithi ikhombisa ushintsho olukhulu kunalapho usebenzisa i-orlistat.
Ku-2012, i-lorcaserin hydrochloride inqobe ukuvunyelwa kwe-FDA futhi yaba yisidakamizwa kadokotela sokukhuluphala kanye nama-comorbidities ahlobene nesisindo. Kodwa-ke, i-Federal Agency iyikhiphile emakethe ngenxa yokwanda kokuqhubeka komdlavuza kubasebenzisi bayo.

Cetilistat

Njenge-lorcaserin (Belviq), i-cetilistat iyisidakamizwa sokulwa nokukhuluphala. Ukuthatha izidakamizwa kuvimbela ama-lipases e-pancreatic, anesibopho sokudiliza i-triglycerides. Ngenxa yalokhu, i-triglycerides ngeke i-hydrolyze ibe ngama-fatty acids mahhala ukuze imuncwe kahle emzimbeni. Ngakho-ke, amafutha azokhishelwa ngaphandle kokugaywa.
I-Cetilistat ingaholela ekwehliseni kuze kufike ku-10% wesisindo somzimba kanye nokwehla okuphawulekayo kumjikelezo okhalweni.
Ngokungafani nemiphumela emibi ye-lorcaserin, izimpawu ezingezinhle ze-cetilistat zihlobene kakhulu nokugaya ukudla. Isibonelo, umuntu uzobhekana nezitulo ezinamafutha nezikhululekile, ukuqothuka, ukuhamba kwamathumbu kaningi, noma ukungasebenzi kwe-fecal.
ICetilistat ayikakutholi ukuvunywa yi-FDA ngoba okwamanje isezigabeni zokuqala zezifundo zabantu. Kuze kube manje, isengezo sinemiphumela ethembisayo. Ukuqhathanisa phakathi kwezibalo zomtholampilo ze-cetilistat ne-orlistat kufakazele ukuthi okwangaphambili kusheshisa kakhulu ukwehla kwesisindo futhi kunokukwazi ukubekezelelana kangcono.
Ukuhlanganiswa kwe-cetilistat ukuthi akusebenzi kwamanye ama-enzyme emathunjini noma ohlelweni lwezinzwa. Leli qiniso lichaza ukuthi kungani linemiphumela emibi kakhulu.

I-Orlistat

Kokubili i-Lorcaserin ne-orlistat usizo ekulahlekelweni kwesisindo. Kodwa-ke, ukusebenza kwabo kwehlukile.
Njenge-cetilistat, i-Orlistat ivimbela okwesikhashana i-gastases ne-pancreatic lipases. Lokhu kuvinjelwa kuphazamisa i-hydrolysis ye-triglycerides ekudleni komuntu, ngakho-ke, wonke amafutha amuncu akhishwa angashintshiwe.
Ngokuya ngezivivinyo zomtholampilo ezitholakalayo, izifundo zabantu zingalahlekelwa isisindo ngokushesha ngenkathi zisebenzisa i-orlistat kunalezo ezikwi-placebo. Ekupheleni kwezinyanga eziyisithupha, kuzoba nezinguquko eziphawulekayo kumjikelezo wokhalo. Ngaphandle kwalokho, ukuthatha lesi sidakamizwa kunciphisa umfutho wegazi kanye nesifo sikashukela sohlobo II.
I-Orlistat iyindlela ehlukile ye-lorcaserin etholakala njengomuthi kadokotela wokwelapha ukukhuluphala kodwa futhi ungathenga ngaphezu kwe-counter. Ngokungafani ne-lorcaserin, le mithi isesigunyeni se-FDA. Izifundazwe eziningi zingathengisa isengezo ngaphandle kwesidingo somuthi ovumelekile. Thatha, isibonelo, e-US, European Union, nase-Australia, ukuthenga i-orlistat kulula njengokukhokhela amateki. I-Orlistat ayinayo imiphumela kwamanye ama-enzyme we-GIT noma uhlelo lwezinzwa.

Ngamafuphi

I-Cetilistat ne-orlistat izindlela ze-lorcaserin zokwelapha ukukhuluphala nokukhuluphala. Kodwa-ke, ukusebenza kwabo kahle kuzokwanda kuphela ngemisebenzi yomzimba kanye nokudla okunama-khalori aphansi. I-Lorcaserin ne-orlistat banciphisa isisindo nobukhulu besinqe kepha ukuyeka imithamo yabo kuzokwenza umsebenzisi abuyisele kufinyelela kuma-35% alokho abakulahlekile.
Kuze kube manje, kuyisengezo se-Cetilistat kuphela esingazange sifinyelele kuhlu lwabamhlophe base-US FDA njengoba kusezilingo zomtholampilo. Ngokuqondene ne-orlistat, ukuyithola kufana nokuthenga i-paracetamol yakho ejwayelekile. Ngokuphambene nalokho, ukwenza i-lorcaserin ithenge cishe akunakwenzeka kusukela i-US Federal Agency isula ukuvunywa kwayo ekuqaleni kwe-2020.
Yonke le mithi emithathu isebenza kahle kepha i-cetilistat inemiphumela ephawulekayo. Ngaphandle kwalokho, inemiphumela emibi embalwa futhi ibekezelela kahle emzimbeni.


Ungayitholaphi i-Lorcaserin kanye nabaPhakathi bayo?

Ungenza i-lorcaserin ithenge ezitolo eziku-inthanethi. Impuphu iyatholakala ngobuningi kubacwaningi nabahlaziyi. Lapho umgomo wakho ukulahla amakhilogremu angeziwe ngenxa yokukhuluphala, ungabheka i-lorcaserin ethengiswa online. Kodwa-ke, ungahle udinge incwadi kadokotela ngenxa yemihlahlandlela eqinile ye-FDA.
Uma ufuna i-lorcaserin noma abaphakathi kwayo, kufanele ubheke ne-CMOAPI ukuthola ukutholakala okuvumelekile kwemikhiqizo emsulwa. Izinhlanganisela zethu zithole isiqinisekiso sekhwalithi.


Okubhekwayo
  1. UTaylor, J., Dietrich, E., noPowell, J. (2013). I-Lorcaserin yokuphathwa kwesisindo. Isifo sikashukela, iMetabolic Syndrome, nokukhuluphala.
  2. Hoy, SM (2013). I-Lorcaserin: Ukubuyekezwa Kwokusetshenziswa Kwayo Ekulawuleni Isisindo Okungapheli. Izidakamizwa.
  3. UHess, R., noCross, LB (2013). Ukuphepha nokusebenza kweLorcaserin ku-Management of Obesity. Imithi Yokuphothula Iziqu.
  4. UBrashier, DB, Sharma, AK, Dahiya, N., noSingh, SK (2014). I-Lorcaserin: I-Novel Antiobesity Izidakamizwa. Ijenali ye-Pharmacology & Pharmacotherapeutics.
  5. UChan, EW et al. (2013). Ukusebenza Nokuphepha kweLorcaserin Kubantu Abakhuluphele ngokweqile: I-Meta-Analysis ye-1-Year Randomized Trials Trials (RCTs) kanye nokuBuyekezwa Okulandelanayo kuma-RCT wesikhathi esifushane. Ukubuyekeza ngokweqile.
  6. INigro, SC, Luon, D., noB Baker, WL (2013). I-Lorcaserin: I-Novel Serotonin 2C Agonist Yokwelapha Ukhuluphele. Ucwaningo Lwanamuhla Lwezokwelapha Nemibono.