Ubururu bwa metilene ku gahinda gakabije no guhangayika: igerageza, imbogamizi n'ibyago byo gukorana n'indi miti

Ubururu bwa metilene bwatangiye guhabwa abarwayi bafite indwara zo mu mutwe mu myaka ya 1890, butangira kugeragezwa mu igerageza ryagenzuwe mu myaka ya 1980, kandi bwakozweho ubushakashatsi mu nyamaswa bugaragaza imirongo y'isano hagati y'ingano n'ingaruka isobanutse mu buryo budasanzwe. Umusomyi ushakisha “ubururu bwa metilene ku gahinda gakabije” asanga ubwo bwoko butatu bw'ibimenyetso buvanze, nta bisobanuro bibutandukanya.

Kubitandukanya ni ingenzi. Ibimenyetso byose byavuye mu igerageza ryagenzuwe ku bantu ku mimerere y'amarangamutima bigizwe n'igerageza ribiri n'igerageza rimwe ryo muri laboratwari ryo guhangana n'ibiteye ubwoba, kandi igerageza ryombi ryanditswe mu gitabo cy'igerageza ryarangiye hashize imyaka irenga icumi. Iyi ngingo isobanura ibyo buri rimwe ryagaragaje. Ntabwo isaba gukoresha ubururu bwa metilene nk'umuti w'indwara y'imimerere y'amarangamutima.

Impamvu irangi ryageze mu bushakashatsi ku mimerere y'amarangamutima

Ubururu bwa metilene ni cyo kinyabutabire cya mbere cyakozwe cyose mu buryo bwa gihanga kigakoreshwa nk'umuti. Monoamine oxidase A, mu magambo ahinnye MAO-A, isenya serotonine, kandi imiti iyibuza gukora isanzwe yemewe mu kuvura agahinda gakabije. Ramsay, Dunford na Gillman bapimye ingaruka ku musemburo MAO-A wo mu bantu wari watunganyijwe, maze batangaza ko igipimo gihoraho cyo kubuza uwo musemburo gukora cyari hafi ya 27 nanomolar, kandi uko kuwubuza gukora gushobora gusubira inyuma. Kuri MAO-B, byasabaga ubwinshi burenga inshuro mirongo itanu. Iyo molekile kandi ibuza imisemburo nitric oxide synthase na guanylate cyclase gukora; ni yo mpamvu isesengura ryo mu 2017 rya Delport na bagenzi be risobanura ingaruka zayo zo kurwanya agahinda gakabije nk'izishingiye ku bice byinshi ikoreraho aho kuba ku rwakiramakuru rumwe.

Ibyo bisobanura impamvu ubushakashatsi ku nyamaswa butanga icyizere ariko bukanagaragaza ibintu bidasanzwe. Mu mbeba, ubururu bwa metilene butuma habaho imyitwarire isa n'iterwa n'imiti irwanya agahinda gakabije mu kizamini cyo koga ku gahato, ariko gusa mu rugero runaka rw'ingano: Eroglu na Caglayan babonye ingaruka hagati ya 15 na 30 mg/kg, ariko ntibazibona kuri 60 mg/kg; umurongo umeze nka U ihindukijwe ni na wo wagaragaye ku myitwarire ijyanye no kugabanuka ko guhangayika. Gutera ingano nto cyane mu gice cy'inyuma cy'ibara ry'ikijuju gikikije umuyoboro wo mu bwonko byagize ingaruka kuri 30 nanomoles, ariko ntibyazigira hanze y'urwo rugero. Ibi ni hormesis, ni ukuvuga ko ingaruka zihinduka bitewe n'ingano, kandi umurongo uteye utyo ntushobora gukoreshwa mu guhanura ingaruka z'ingano zisumbuyeho.

Igerageza ryo mu myaka ya 1980 n'ingano yiswe placebo ishobora kuba itari yo

Naylor na bagenzi be bakoze igerageza ry'imyaka ibiri aho abarwayi bahinduranyaga imiti kandi haba bo cyangwa abashakashatsi batazi ingano yari yatanzwe ku barwayi 31 bafite indwara ya bipolar, bagereranya 300 mg ku munsi na 15 mg ku munsi, mu gihe bakomezaga gufata lithium. Cumi na barindwi bararirangije, kandi agahinda gakabije kari kagabanutse ku buryo bufite ubusobanuro mu mibare y'ubushakashatsi ku ngano yo hejuru.

Uburyo igerageza ryateguwe burimo ikibazo gikwiye gusobanuka, kuko gikunda kugaruka. Ingano ya miligarama cumi n'eshanu ku munsi yatoranyijwe nk'iy'itsinda rya “placebo”, hafashwe ko itagira igikorwa. Nyuma, abanditsi banditse ko bari bafite “ugushidikanya ku kuba umuti wari warahishwe koko, n'ukutamenya neza niba 15 mg z'ubururu bwa metilene ku munsi zashoboraga gufatwa nka placebo.” Ubururu bwa metilene buhindura inkari ubururu buvanze n'icyatsi, bityo buri murwayi wahinduranyaga ingano zombi yafata irangi rigaragara ko rifite igikorwa muri buri gihe cy'igerageza. Niba ingano nto yari ifite igikorwa, iryo gerageza ryagereranyaga ingano ebyiri zombi zifite igikorwa.

Igerageza rigufi ryagereranyije 15 mg ku munsi na placebo nyayo ku barwayi bafite agahinda gakabije cyane mu gihe cy'ibyumweru bitatu, ku barwayi 35, maze rigaragaza ko abafataga ubururu bwa metilene barushijeho kumererwa neza ku buryo bufite ubusobanuro mu mibare y'ubushakashatsi. Ibyumweru bitatu n'abarwayi mirongo itatu na batanu bitanga ikimenyetso nyacyo, ariko gito.

Igerageza ryo guhinduranya ingano ku ndwara ya bipolar: ibimenyetso bikomeye kurusha ibindi mu bantu

Igerageza ritanga amakuru menshi kurusha ayandi ni ubushakashatsi bwo mu 2017 bwa Alda na bagenzi be, bwanditswe nka NCT00214877. Bwarimo abantu mirongo itatu na barindwi bafite indwara ya bipolar I cyangwa II, bose bafataga lamotrigine nk'umuti wabo w'ingenzi wo gutuma imimerere y'amarangamutima idahindagurika, abenshi bakaba bari bagifite ibimenyetso byoroheje cyangwa biciriritse. Igerageza ryari iryo guhinduranya ingano, aho abarwayi n'abashakashatsi batamenyaga ingano yari yatanzwe: 15 mg ku munsi mu mezi atatu ugereranyije na 195 mg ku munsi mu mezi atatu, bikurikirana mu buryo bwatoranyijwe ku bw'amahirwe. Abanditsi basobanuye neza impamvu bahisemo kugereranya n'ingano nto: “Twahisemo ubu buryo kuko ubururu bwa metilene buhindura ibara ry'inkari, bityo ntitwashoboraga gukoresha placebo isanzwe.”

Mu isesengura ry'abarwayi 27 barangije igerageza:

• Agahinda gakabije kagabanutse kurushaho ku ngano yo hejuru, ubunini bw'ingaruka bukaba 0.71 ku gipimo cya Hamilton Depression Rating Scale (95% CI 0.15 to 1.25, P = 0.034) na 0.80 ku gipimo cya Montgomery-Asberg Depression Rating Scale (95% CI 0.27 to 1.30, P = 0.020).
• Guhangayika kwagabanutse kurushaho ku ngano yo hejuru, ubunini bw'ingaruka bukaba 0.79 ku gipimo cya Hamilton Anxiety Rating Scale (95% CI 0.22 to 1.33, P = 0.028). Ibipimo by'ibimenyetso byo guhangayika byo mu mutwe ni byo byagaragaje izo ngaruka; ibimenyetso byo guhangayika bigaragara ku mubiri byagize ubusobanuro mu mibare y'ubushakashatsi gusa mu isesengura ry'abari bagenewe kuvurwa bose.
• Ibimenyetso bya mania byakomeje kuba bike kandi bidahinduka, nta guhindukira kugana kuri hypomania cyangwa mania.
• Ubushobozi bwo gutekereza ntibwahindutse muri kimwe mu bizamini bitandatu, birimo kwiga amagambo, ubushobozi bwo gutegura no kugenzura ibikorwa, n'ububiko bwo kwibuka ibyabaye.

Icumi muri 37 bavuye mu igerageza, umwe kubera inkari z'ubururu, umwe kubera ko guhangayika kwiyongereye, n'umwe nyuma y'uko uburwayi bwe bwiyongereye. Ingaruka zitifuzwa zari iz'igihe gito kandi zoroheje, ahanini kumva hotsa mu nzira z'inkari, impiswi, isesemi no kubabara umutwe. Abantu bari hagati ya 20 na 27 bafataga umuti urwanya agahinda gakabije cyangwa umuti urwanya ibimenyetso by'indwara zo mu mutwe zitera gutakaza ukuri mu gihe cyose cy'igerageza, kandi nta ngaruka z'uburozi bwa serotonine ryatangaje.

Abitabiriye ntibari bafite agahinda gakabije cyane. Amanota yo mu ntangiriro yari 12.7 ku gipimo cya Montgomery-Asberg, kigera kuri 60, na 7.6 ku gipimo cya Hamilton kigizwe n'ingingo 17: byari ibimenyetso bisigaye mu barwayi bari bamaze gutuza, ntabwo yari indwara y'agahinda gakabije yo ku rwego rukomeye. Isesengura rishingiye ku buryo buteguye ryo mu 2021 ku kuvura guhangayika mu ndwara ya bipolar ibimenyetso byayo byagabanutse, ryakozwe n'abashakashatsi bigenga, rishyira iri gerageza muri bibiri gusa by'imiti byagaragaje umusaruro mwiza ku guhangayika mu igerageza icumi ryasuzumwe ryagabanyaga abantu mu matsinda ku bw'amahirwe. Rinavuga ko umubare munini w'abavuyemo n'ingaruka zitifuzwa zigaragara bishobora kuba byarabujije guhisha neza umuti watanzwe.

Igerageza rimwe ryagenzuwe ku guhangayika mu bantu

Igerageza rya mbere ryagenzuwe ku bantu ku bururu bwa metilene no guhangayika ntiryari iryo kuvura, ahubwo ryari iryo gushimangira ibyo umuntu yibuka. Telch na bagenzi be batoranyije abantu bakuru bagiraga ubwoba bukomeye bwo kuba ahantu hafunze; buri wese yakoze inshuro esheshatu z'igerageza ryo guhangana n'ubwoba, buri nshuro ikamara iminota itanu mu cyumba gifunze. Ako kanya nyuma yaho, kandi nyuma yaho gusa, bahawe 260 mg z'ubururu bwa metilene cyangwa placebo, haba bo cyangwa abashakashatsi batazi icyatanzwe. Nyuma y'ukwezi, bongeye gukorerwa ikizamini mu kindi cyumba kugira ngo harebwe niba ubwoba bwaragarutse.

Ibyavuye mu igerageza byatandukanyije itsinda. Abasoje igihe cyo guhangana n'ubwoba bafite ubwoba buke bagumanye iryo terambere neza cyane ku bururu bwa metilene, naho abasoje bagifite ubwoba bagize umusaruro mubi kurusha abafashe placebo. Umuti usa n'ushimangira ibyo umuntu yize byose, bityo igihe cyo guhangana n'ubwoba cyashimangiye ubwoba cyatumye ubwoba bwiyongera. Kwibuka imimerere ibintu byabereyemo byarushijeho kuba byiza uko byagenda kose, bikemeza ko umuti wageze mu bwonko. Ingano imwe, mu buryo bumwe bw'igerageza, yatanze ibisubizo bihabanye bitewe n'ikintu kimwe gusa; ibyo ni byo bisobanurwa mu ngingo ivuga impamvu uko igihe cyo guhangana n'ibiteye ubwoba kigenda ari byo bigena iki gisubizo.

Igerageza kuri PTSD n'umwanzuro w'abashakashatsi bigenga

Ubushakashatsi bwagutse bwakurikiyeho ni igerageza rya Zoellner na bagenzi be ku ndwara idakira iterwa n'ihungabana nyuma y'ibintu bibabaje, PTSD, ryagabanyaga abarwayi mu matsinda ku bw'amahirwe, ryanditswe nka NCT01188694. Abarwayi mirongo ine na babiri bahawe ibihe bitanu byo guhangana n'ibyabahungabanyije babitekereza, kimwe buri munsi, bigakurikirwa na 260 mg z'ubururu bwa metilene; cyangwa gahunda imwe igakurikirwa na placebo; cyangwa bashyirwa ku rutonde rw'abategereza, nyuma bagahabwa ubuvuzi busanzwe bwo guhangana n'ibyabahungabanyije mu gihe kirekire.

Ku gipimo cy'ibanze cy'umusaruro, ari cyo PTSD Symptom Scale cyapimwe n'umugenzuzi wigenga, ubururu bwa metilene ntibwagaragaje itandukaniro na placebo. Ibisubizo byashyizwe mu gitabo cy'igerageza byerekana amanota ya nyuma yo kuvurwa ya 17.10 ku bururu bwa metilene ugereranyije na 14.67 kuri placebo, yombi yagabanutse avuye hafi kuri 32 mu ntangiriro. Itandukaniro ryari rishyigikiye placebo.

Ibisubizo bibiri by'inyongera byagaragaje ibinyuranye n'ibyo. Abafashe ubururu bwa metilene benshi kurushaho babaruwe nk'abitabiriye neza ubuvuzi, umubare w'abagomba kuvurwa kugira ngo haboneke umwe wungukiramo ukaba 7.5, kandi ubuzima bwa buri munsi bwabaye bwiza kurushaho, ubunini bw'ingaruka bukaba 0.58. Akamaro kashingiraga ku bushobozi bwo kugumana amakuru mu bwenge no kuyakoresha ako kanya, aho gushingira ku mpinduka mu myumvire ijyanye n'ihungabana.

Nyuma yaho, isesengura rishingiye ku buryo buteguye ryo mu 2023 ku guhindura ububiko bwo kwibuka hakoreshejwe imiti mu buvuzi bwo mu mutwe bwibanda ku ihungabana ryashyize ubururu bwa metilene mu itsinda ry'ibinyabutabire bitagaragaje ingaruka zifite ubusobanuro mu mibare y'ubushakashatsi ku kugabanya ibimenyetso bya PTSD. Uwo ni wo mwanzuro w'abashakashatsi bigenga muri iki gihe: ntibyemejwe ko budakora, ntibyemejwe ko bukora, kandi ibimenyetso ntibikomeye bihagije kugira ngo bukoreshwe hanze ya gahunda y'ubushakashatsi.

Ibitandukanya amatsinda y'abakorewe ubushakashatsi

Soma inkingi ya nyuma uyigereranya n'iya kabiri, aho kuyigereranya n'incamake y'ubushakashatsi.

Nta na rimwe muri aya magerageza ryasuzumye ubururu bwa metilene nk'ubuvuzi bwonyine bw'indwara y'agahinda gakabije yo ku rwego rukomeye, kandi ClinicalTrials.gov nta bushakashatsi bushya bwo kugerageza ubuvuzi ku ndwara y'agahinda gakabije cyangwa yo guhangayika igaragaza buruta ayo abiri yavuzwe haruguru, yanditswe mu 2003 no mu 2009. Umuntu wese uvuga ko ubururu bwa metilene ari umuti wemejwe wo kurwanya agahinda gakabije aba avuga igitekerezo gishingiye ku buryo bushoboka bwo gukora, gishyigikiwe n'igerageza rito rimwe ryatanze umusaruro mwiza. Nta gerageza ryigeze ritangaza ko habayeho guhindukira kugana kuri mania.

Ibyago byo gukorana n'indi miti ni byo bisaba kwitonda

Ubururu bwa metilene bubuza MAO-A gukora. Ibyo ni byo bituma bushishikaza mu bushakashatsi ku mimerere y'amarangamutima, kandi ni na byo bituma buba akaga iyo bufashwe hamwe n'indi miti yongera igikorwa cya serotonine, harimo imiti myinshi irwanya agahinda gakabije. Kongera umuti ubuza MAO gukora ku muti ubuza isubiramufatwa rya serotonine byongera igikorwa cya serotonine binyuze mu nzira ebyiri zitandukanye, kandi iyo miti ifashwe hamwe ishobora gutera uburozi bwa serotonine, rimwe na rimwe bushobora kwica.

Igicuruzwa gitangwa mu mutsi gifite umuburo wihariye uri mu gasanduku kuri ibyo. FDA yaburiye kuri iyo mikoranire mu 2011, nyuma iza kwibanda cyane ku gutanga umuti mu mutsi no ku miti imwe n'imwe irwanya agahinda gakabije. Ubururu bwa metilene kandi buri mu bintu bigize imiti imwe n'imwe igabanya ububabare bwo mu nzira z'inkari; ibyo ni byo byatumye nibura habaho ikibazo kimwe nyuma yo gufata umuti mu kanwa ku murwayi wafataga imiti myinshi yongera igikorwa cya serotonine. Amabwiriza ku mikoranire y'imiti asobanura ibyo byago hakurikijwe icyiciro cy'umuti n'inzira unyuzwamo.

Nta na rimwe muri ya magerageza abiri ku mimerere y'amarangamutima rivuguruza izo mpungenge, ariko nta na rimwe rinatanga umwanzuro uzikemura. Yombi yakorewe ku barwayi abenshi bafataga indi miti y'indwara zo mu mutwe, kandi nta na rimwe ryatangaje uburozi bwa serotonine. Ibyo birahumuriza mu magerageza mato akurikiranwa kandi afite abo atemerera kuyitabira, ariko ntibigaragaza ko kuvanga iyo miti umuntu abyihitiyemo bifite umutekano. Uburozi bwa serotonine bugaragazwa no guhagarika umutima cyangwa kwitiranya ibintu, umuriro cyangwa kubira ibyuya byinshi, umutima utera vuba, gutengurwa, gukomera kw'imitsi no kwinyagambura utabishaka, kandi si ikibazo umuntu akwiye kwisuzumira mu rugo.

Isano bifitanye n'urwego rw'ubuziranenge bw'igicuruzwa

Amacupa abiri afite ikirango kimwe ashobora gutandukana mu bindi biyagize. Kubahiriza ibisabwa biri mu nyandiko yihariye ya USP ni byo umuguzi ashobora kugenzura, kandi igicuruzwa kitabyubahiriza gishobora kuba ari icyo ku rwego rwo gusiga imyenda. Gishobora kuba kirimo umwanda w'ibinyabutabire birimo karubone nka Azure B na Azure C, ibisigazwa by'imiti isheshesha, n'ibyuma biremereye ku rugero ibisabwa ku miti bigabanya.

Abacuruzi benshi bakoresha imvugo ngo “cyapimwe n'urundi ruhande rwigenga” bapima ibyuma biremereye gusa, bakerekana icyo gipimo kimwe nk'aho cyubahiriza ibisabwa byose. Blupreme ipima ibisabwa byose bya USP: kumenya neza ikinyabutabire, ubuziranenge, umwanda w'ibinyabutabire birimo karubone, ibisigazwa by'imiti isheshesha, umwanda w'ibinyabutabire by'ibanze, ibisigara nyuma yo gutwikwa, imipaka ntarengwa ya mikorobe, n'uburozi bwo imbere muri bagiteri. Kandi itangaza icyemezo cy'isesengura kuri buri cyiciro cy'ibicuruzwa cyakorewe icyarimwe. Kugisoma neza bisaba kugenzura nimero y'icyiciro, laboratwari, uburyo bwo gupima n'imipaka ntarengwa, aho gushaka gusa ikimenyetso cyo gutsinda.

Umwanzuro uvugisha ukuri

Igerageza kuri bipolar ni ryo ritanga ibimenyetso bikomeye kurusha ibindi mu bantu, kandi rigaragaza ingaruka ziciriritse z'umuti w'inyongera ku bimenyetso bisigaye mu itsinda ry'abarwayi bari bamaze gutuza kandi bafite ibimenyetso byoroheje. Igerageza ku gahinda gakabije cyane ryamaze ibyumweru bitatu kandi ryari ririmo abarwayi mirongo itatu na batanu. Igerageza ku bwoba bwo kuba ahantu hafunze rigaragaza ingaruka nyazo ku gushimangira ibyo umuntu yibuka, zishobora gukora mu byerekezo byombi. Igerageza kuri PTSD ntiryasubiyemo umusaruro wari witezwe ku gipimo cyaryo cy'ibanze. Nta kindi cyageragejwe kuva icyo gihe.

Uko ni ko uburyo bwo gukora butanga icyizere buba bumeze mbere y'uko buhinduka ubuvuzi; kandi ni na ko bigenda iyo ikinyabutabire kigurishwa gishingiye ku mbaraga z'uburyo gikora aho gushingira ku byavuye mu bushakashatsi. Niba ufata umuti urwanya agahinda gakabije wandikiwe, umuti ubuza MAO gukora, umuti wo mu bwoko bwa opioid, cyangwa undi muti uwo ari wo wose wongera igikorwa cya serotonine, urwo rutonde rugomba kuza mbere mu kiganiro, mbere y'ikibazo icyo ari cyo cyose kijyanye n'ingano. Ububiko bwose bw'ubushakashatsi butondeka igerageza n'ubushakashatsi bw'igerageza bishyigikira ibyo bivugwa. Tangirira ku ncamake y'ingaruka zitifuzwa n'ibihe bituma umuti udakwiye gukoreshwa no ku isesengura ry'ibishyigikiwe n'ubushakashatsi ku bantu, maze usome ibimenyetso byihariye ku ndwara ya bipolar niba ari yo wasanganywe. Ntugahagarike umuti wandikiwe kugira ngo uwusimbuze uwo kugerageza.