Te Kikorangi Metilīni me te Mate Rangirua: He Tirohanga ki ngā Rangahau Haumanu

Te whakarāpopototanga poto

Kua roa ake te kikorangi metilīni e rangahaua ana mō te mate rangirua i tā te nuinga e mōhio ana. I tīmata i ngā tau 1970, i te rapunga a ngā kairangahau i ētahi rongoā hei whakakapi, hei tāpiri rānei ki te lithium. He iti te pūtake taunakitanga katoa: kotahi te rangahau raupapa kēhi kāore i huna, e rua ngā whakamātautau whakataurite o mua, me tētahi rangahau hou, matapōkere, whakawhiti maimoatanga. Ko te tohu ōrite puta noa, ko te pai ake o ngā tohumate pāpōuri me ngā tohumate e toe ana i te tāpiritanga o te kikorangi metilīni ki te maimoatanga o nāianei. Kāore tētahi rangahau i whakaatu i te pānga whakaiti mania, ā, kāore tētahi i whakaputa i te tohu mārama o te whakawhitinga ki te mania. Heoi, he iti rawa ngā rōpū kia tau ai te pātai mō taua whakawhitinga. Me pānui te tangata e aromatawai ana i tēnei pūhui i ēnei hei rangahau maimoatanga tāpiri, kaua hei taunakitanga mō te maimoatanga ki te rongoā kotahi anake. Me āta whai whakaaro hoki ki ngā whakatūpato mō ngā pāhekoheko i mua i te whakatau i tētahi whakamahinga.

He aha i aro wawe ai ki te mate rangirua

Ehara te take i te rite o te kikorangi metilīni ki tētahi rongoā whakatau wairua tikanga noa. Ki tōna hanganga, he rite ki ngā phenothiazine. I whakapae ngā kairangahau o mua ka taea e ia te whakaheke ā-matū i te vanadate o te wē toto ki tētahi āhua ngoikore ake, ka panoni ai i te mahi a te ATPase konutai-pāhare pāporo, e whakaarotia ana he wāhi tōna i ngā huringa wairua. Hei whakamātau i tēnei ariā, i maimoa a Naylor me ōna hoa i ngā tūroro tokorua he huringa wairua haere tonu ō rāua, ā, i kitea he roa ake ngā wā tau o te wairua. Nā tēnei i whakatenatena ngā mahi i whai mai. E whakamārama ana te kōrero hītori a Howland mō te kikorangi metilīni i te mātai hinengaro i te horopaki o tēnei mahi, me te whai i te pūhui mai i tōna tūranga hei pūhui mātāmua o te phenothiazine ki tōna whakamahinga hei matū whakamātau e pā ana ki te hinengaro.

Nā ngā rangahau tikanga mahi o muri mai i whakahāngai anō te take ki te mahi a ngā mitokōria me te taurite hāoratanga–whakahekenga. Kua whakaarotia he wāhi tō te mahi hē a ngā mitokōria i te mate rangirua, i runga i ngā rangahau whānau, ngā kitenga whakapuaki ira i muri i te matenga, me ngā tauira kararehe pēnei i te kiore he panonitanga tō te ira POLG1. Ko ōna āhuatanga e rite ana ki te mate rangirua ka urupare wāhanga ki te lithium. E whakapae ana te arotake a Alda o 2019 mō te kikorangi metilīni i ngā mate io-hinengaro, nā te kaha o te pūhui ki te kawe irahiko mā tua atu i ngā wāhi aukati o te mekameka kawe irahiko, me te whakaiti i te rerenga o ngā momo hāora hohe, he whai take ia hei ārahi i te rangahau mō tētahi matū whakarerekē i te mahi mitokōria. Ka tāpiri tētahi arotake mō te kikorangi metilīni hei rongoā pāpōuri pea i te aukatinga MAO-A, te aukatinga o te nitric oxide synthase me te guanylate cyclase, me ngā pānga whakaiti mumura ki tēnei whakamārama mō ngā tikanga mahi. He whakapae tonu ēnei tikanga mahi. Ko te pātai haumanu, he aha i inea e ngā whakamātautau, ā, i raro i ēhea āhuatanga.

Ngā whakamātautau, takitahi

Te raupapa kēhi a Narsapur rāua ko Naylor: ngā tūroro kāore i urupare ki te maimoatanga, he maimoatanga kāore i huna

Ko te pūrongo tuatahi he raupapa kāore he rōpū whakataurite, o ngā tūroro 24 e mate mauroa ana, e tino māuiui ana rānei. I whakawhiwhia ki te kikorangi metilīni hei tāpiri, i te 200, i te 300 mg rānei ia rā, mō ngā wā mai i ētahi rā ki tua atu i te kotahi tau. Tekau mā iwa i pāngia e te mate rangirua (mania-pāpōuri), ā, i whakatauria kua tino pai ake te āhua o te 14 o aua tūroro 19, arā, he urupare 74 ōrau. Kāore i urupare ngā tūroro tokotoru i rangiruatia tō rātou tātaritanga mate rangirua.

Me whakaaro ki tēnei hei whakaputa whakapae, kaua hei raraunga mō te whaihua. Kāore he tohatoha matapōkere, kāore i huna ngā maimoatanga, kāore he tauine paerewa, ā, kāore i tino pūrongotia ngā rongoā e whakamahia kētia ana. Ko te tatauranga 74 ōrau mai i tētahi raupapa kāore i huna, mō ngā tūroro kāore i urupare ki te maimoatanga, e whakaata ana i te whakatau a te kaitirotiro me te kōwhiringa tūroro, pērā anō i ngā pānga ā-rongoā.

Naylor me ōna hoa 1986: he whakamātautau ārai e whakawhiti ana i ngā maimoatanga mō te rua tau, me te lithium

Ko tēnei te rangahau nui rawa te whāinga o ngā rangahau tōmua: he whakamātautau rua tau, matapōkere, huna-rua, whakawhiti maimoatanga, i ngā tūroro 31 e pāngia ana e te mate rangirua. I whakaritea kia whiwhi ia kaiuru i te 300 mg ia rā mō tētahi tau, me te 15 mg ia rā mō tērā atu tau, i te raupapa matapōkere. Ko te horopeta 15 mg te whakataurite, i kōwhiria matua nā te mea ka panoni te tae o te mimi, e kore ai e taea te huna i tētahi rongoā whakataruna tino kore pānga. Ko te mea nui, i mau tonu ia kaiuru ki te lithium puta noa, nō reira he maimoatanga ārai tāpiri tēnei mai i te tīmatanga.

Tekau mā whitu o te 31 i whakaoti i ngā tau e rua. I roto i te hunga i whakaoti, he tino iti iho te taumaha o ngā tohumate pāpōuri i te tau 300 mg i tō te tau 15 mg, engari kāore te taumaha o ngā tohumate mania i rerekē i waenga i ngā horopeta. I pūrongotia he iti ake ngā whakaurunga ki te hōhipera i te wā o te whakamātautau i ērā i mua. Heoi, e kī ana te arotake o muri mai a Alda i pā tēnei ahakoa i ngā wā 15 mg, e uaua ake ai te whakamāori i ngā hua. Nā ngā kairangahau tonu ngā ngoikoretanga i tohu: he rōpū iti, 45 ōrau i whakarere i te rangahau, he tauine aromatawai māmā, he huna maimoatanga e rangiruatia ana, me te kore mōhio mēnā kāore rawa he pānga ā-rongoā o te 15 mg. I tika taua āwangawanga whakamutunga, e whakaahuatia ana i raro nei.

Te rangahau pāpōuri horopeta iti a Naylor: he aha i whai pānga ai pea te “rongoā whakataruna”

I muri mai, ka whakatauritea i tētahi rangahau huna-rua mō te toru wiki te 15 mg ia rā ki tētahi rongoā whakataruna kore pānga, i ngā tūroro 35 e tino pāngia ana e te mate pāpōuri. I kitea he tino pai ake te kikorangi metilīni. Ko te nuinga o tēnei rōpū he pāpōuri kotahi te pou, ehara i te whakamātautau mate rangirua, nō reira kei roto kē i ngā taunakitanga whānui mō te pāpōuri, kaua i te kāwai mate rangirua. Ko tōna hiranga mō ngā kaipānui e aro ana ki te mate rangirua, ko te tikanga rangahau: ko te horopeta 15 mg i whakamahia hei whakataurite i ngā whakamātautau whakawhiti maimoatanga e rua, kua toa ake i te rongoā whakataruna kore pānga. Nō reira, tērā pea ka whakaiti te whakataurite maimoatanga ki te 15 mg i te rerekētanga katoa ki te kore maimoatanga. Waihoki, ko te tikanga kāore tētahi o ngā whakamātautau o mua i whai rōpū rongoā whakataruna tūturu.

Alda me ōna hoa 2017: te whakamātautau hou o te maimoatanga tāpiri, whakawhiti maimoatanga

Ko te rangahau tino pakari tae noa ki tēnei wā i tohatoha matapōkere i ngā pakeke 37 he mate rangirua I, II rānei, me ngā tohumate e toe ana, ki te kikorangi metilīni 195 mg ia rā, ki te 15 mg ia rā rānei. I whakawhitihia ngā maimoatanga, mō te 13 wiki ia maimoatanga. I mārama te whakatakoto he maimoatanga tāpiri tēnei: kua tau te āhua o ia kaiuru ki te lamotrigine mō te toru marama neke atu, ā, i haere tonu taua rongoā. I whakaaetia hoki te lithium, te divalproex, ngā rongoā ārai mate hinengaro, me ngā rongoā pāpōuri, ki te mau tonu ngā horopeta. Kei PubMed 27284082 te whakamātautau e rārangitia ana. He māmā ki te āhua taumaha ngā tohumate i te tīmatanga, ko ngā kaute toharite pāpōuri Hamilton kei te takiwā o te 7.6, ko ngā kaute Montgomery-Asberg kei te takiwā o te 12.7.

I tautoko ngā hua i te 195 mg mō ngā inenga pāpōuri me te māharahara. I roto i te hunga i whakaoti, ko ngā rahinga pānga kei te takiwā o te 0.71 i te tauine pāpōuri Hamilton, te 0.80 i te tauine Montgomery-Asberg, me te 0.79 i te tauine māharahara Hamilton. He whai tikanga ā-tatauranga ia hua. I te tātaritanga o ngā tūroro 37 katoa, mā te kawe whakamua i te inenga whakamutunga i kitea, i puta anō ngā hua whai tikanga e rite ana. I noho iti, i noho pūmau hoki ngā kaute mania, kāore he pānga maimoatanga. Kāore hoki te huinga whakamātautau hinengaro i whakaatu i tētahi painga whai tikanga mō te mahara ā-kupu, te whakahaere hinengaro, ngā inenga aro rānei. Tekau ngā kaiuru i wehe atu mō ngā take tae atu ki te kino haere o ngā tohumate mate rangirua, te māharahara, te pupuri wai, me te tango i tō rātou whakaaetanga. Ko ngā pānga kino te nuinga he wera rangitahi i te mimi, he whakararu i te puku me ngā whēkau, me te ānini.

Te ripanga whakamātautau haumanu: ngā mea i tino whakamātauria

Te pānui pono i te tauira o ngā hua

E toru ngā kitenga e tū tonu ana ahakoa ngā herenga. Tuatahi, he ōrite te aronga o te pānga: i pai ake ngā tohumate pāpōuri me ngā tohumate e toe ana ki te horopeta teitei ake i ngā rangahau whakataurite mate rangirua e rua, ā, he āhua nui ngā rahinga pānga i te whakamātautau hou. Tuarua, kāore he mea i ēnei tuhinga rangahau e tautoko ana i te kerēme whakaiti mania. Kāore te whakamātautau i aro pū ki te mania i kitea he painga, ā, kāore ngā rangahau whakawhiti maimoatanga i kitea he rerekētanga mania. Ko tēnei he kore taunakitanga mō te whaihua ki te whakaiti mania, ehara i te taunakitanga mō te whakatau wairua i ngā pou e rua. Tuatoru, kāore i puta he tohu mania nā te maimoatanga, engari he iti te kaha o taua kōrero. I te tīmatanga, i tata ki te kore ngā kaute mania, ā, he tekau, he tekau noa iho ngā tāngata i whiwhi i te maimoatanga. Nō reira, kāore e taea e ēnei rangahau te kite i tētahi tūraru whakawhitinga he nui tōna hiranga haumanu. Ko te kōrero tika, kāore i kitea he tohu whakawhitinga, kaua ko te kī kua whakakorea te tūraru whakawhitinga.

E rua ngā raruraru tikanga rangahau e tika ana kia whakanuia, nā te mea ka pā ki te pūtake taunakitanga katoa. I ngoikore te huna maimoatanga i runga tonu i te hanganga o ia rangahau whakawhiti maimoatanga, nā te mea ka panoni te kikorangi metilīni i te tae o te mimi. I kōwhiria te horopeta iti hei whakataurite hei tāwhai tonu i taua pānga, me te whakapae kāore ōna pānga ā-rongoā. Ā, i hē taua whakapae: i toa ake te horopeta iti i te rongoā whakataruna kore pānga mō te pāpōuri. Nō reira, ko ngā whakataurite matua he whakataurite horopeta i waenga i ngā maimoatanga e rua he pānga pea tō ia maimoatanga, ehara i te whakamātautau rongoā ki te rongoā whakataruna. He uaua te whakamāori i ngā rahinga pānga i inea pēneitia, ā, kāore e taea te whakakotahi ki ngā whakamātautau paerewa o ngā rongoā pāpōuri e whakatauritea ana ki te rongoā whakataruna.

He mea nui te pupuri ki te whānuitanga tika i konei. He whakamātautau mate rangirua ēnei, me ngā inenga putanga mate rangirua, ā, kaua e whakaranua ki ngā taunakitanga nō ētahi atu taupori. Me tiro motuhake ngā kaipānui e hiahia ana ki ngā rangahau e pātata ana ki ngā kitenga mō te māharahara, ngā rangahau mahi hinengaro, me te whakaaturanga haumaru me ngā pāhekoheko, nā te mea he rerekē ngā hoahoa rangahau me ngā whakaaro mō te tūraru o ia kaupapa.

Te horopaki haumaru mō te whakamahi rongoā maha i te mate rangirua

E rua ngā whakatūpato e hāngai tika ana ki ngā tūroro mate rangirua, he maha ka tohua ki ngā rongoā e pā ana ki te serotonin. Ko te kikorangi metilīni me tōna hua pākia, te Azure B, he tino kaha ki te aukati MAO-A, ā, ka taea taua aukatinga te whakahoki. Ka whakamahia ngātahitia ki ngā SSRI, ngā SNRI, me ētahi atu rongoā e pā ana ki te serotonin, ka taea te whakaoho i te mate serotonin. Tata ki te katoa o ngā kēhi paitini kua whakaputaina i pā ki te kikorangi metilīni i tukuna mā roto i te ia toto. I whakaaetia ngā rongoā pāpōuri i te whakamātautau mate rangirua hou mō te 20 o ngā kaiuru 37, kāore hoki he takahanga kino e pā ana ki te serotonin. Heoi, kāore taua wheako iti e whakakore i te whakatūpato pāhekoheko, ā, kei ngā tapanga o nāianei mō te hua tuku ā-ia toto he whakatūpato pouaka mō tēnei take. Hei take motuhake, ko te ngoikoretanga glucose-6-phosphate dehydrogenase he take kia kaua tēnei rongoā e whakamahia, nā te mea ka taea e te kikorangi metilīni te whakaoho i te pakarutanga o ngā pūtau toto whero. I aukatia aua tūroro i te whakamātautau hou. Me whai te tangata e whakakotahi ana i ēnei rongoā i te tirotiro a tētahi mātanga haumanu; he mātai rongoā tēnei e taea ai ngā raruraru tūturu, ehara i te pāhekoheko tāpiringa kai kore kino.

Kei hea te pātai e tū ana ināianei

Ko ngā tuhinga rangahau mō te kikorangi metilīni i te mate rangirua he iti, he tawhito, he tohu whakapae noa, me tētahi rangahau whakataki hou e tika ana te kounga. Ko te whakarāpopototanga pono: ko te kikorangi metilīni hei tāpiri, i te takiwā o te 195 ki te 300 mg ia rā, i whakaiti anō, i whakaiti anō i ngā tohumate pāpōuri me ngā tohumate e toe ana i ngā rōpū iti. Kotahi te wā i kitea he tohu mō te māharahara, kāore he painga mō te mahi hinengaro i kitea, kāore he pānga whakaiti mania i kitea, ā, kāore he tohu whakawhitinga ki te mania i kitea e taea ana te kite e ēnei rahi rōpū. Kāore anō kia mahia he whakamātautau nui ake me te rongoā whakataruna tūturu hei whakataurite, ngā taupori e pāngia ana e te pāpōuri whakapeka o te mate rangirua, te aroturuki whakawhitinga ki te mania kua whakaritea i mua, me ngā tikanga huna maimoatanga e tika ana. Kia mahia rā anō aua rangahau, ka noho te kikorangi metilīni hei maimoatanga tāpiri e rangahaua tonutia ana i tēnei horopaki: he nui tōna whakamere kia rangahaua anō, engari he iti rawa ngā taunakitanga hei tautoko i ngā whakatau.