Zvinodzvinyirira Zvinodhaka Zvinogona Kuita Nenzira Yakare Isingazivikanwe

Zvemukati

• SSRIs Inokosha Inoverengwa
• Chikumbiro chezvePfungwa Dzakakwana Psychiatry

Pfungwa Dzinokosha: Chidzidzo chitsva chinetso chakambobata pfungwa dzekuti mishonga yekudzvinyirira inoshanda sei. Iyi tsvagiridzo inoratidza kuti inononoka-kuita SSRIs uye inokurumidza-kuita ketamine inosunga yakanangana nehuropi-yakatorwa neurotrophic factor (BDNF) receptor uye inosimudzira kushushikana-kurerutsa neuronal plasticity pasina rubatsiro kubva serotonin kana glutamate.

Chidzidzo chitsva chenyika dzese (Casarotto et al., 2021) vakabatana vachitungamirwa nemunyori mukuru Eero Castrén weUniversity yeHelsinki's Neuroscience Center pamwe nevamwe vaanoshanda navo muDhipatimendi reFizikiki vanoongorora mashandisiro anoita mishonga yekudzvinyirira mitatu - fluoxetine (SSRI inotengeswa pasi pezita rezita. Prozac), imipramine (tricyclic antidepressant), uye inokurumidza kuita ketamine ("nyowani kurapwa" kwekurapa kusingagadziriswe kurapwa; inongowanikwa chete kuhofisi yechiremba kana kiriniki) -yanana neBDNF receptor inozivikanwa seTrkB. Iri pepa rekuvhura-rekuwana rakaburitswa muna Kukadzi 18 mumagazini inoongorora-vezera Sero .

Nhoroondo, inosarudza serotonin reuptake inhibitors (SSRIs) uye tricyclic antidepressants 'mhedzisiro yaifungidzirwa kuti yakadzika midzi mukugona kwavo kuchengetedza yakawanda serotonin uye norepinephrine inowanikwa kuhuropi nekuwedzera huwandu hweaya maurotransmitter mune synaptic gap. Pamwe chete neiyi tambo, iyo antidepressant mhedzisiro ye ketamine yaifungidzirwa kuti inoshanda zvakanyanya nekudzivirira glutamate receptors.

Sezvineiwo, iyo mitatu mishonga yekudzvinyirira yakaongororwa muchidzidzo chino (fluoxetine, imipramine, uye ketamine) yakabatana neTrkB pasina hazvo kuwedzera kana kudzivirira mamwe maurotransmitter senge serotonin, norepinephrine, kana glutamate.

Kunyangwe kutsvagurudza kwakapfuura kwakaratidza hukama pakati peanodzvinyirira anowedzera neurotrophic zvinhu zvakaita seBDNF, iyo inoita basa mukugadzirisa neuroplasticity, kusvikira zvino, vaongorori vakafunga kuti mishonga yekudzvinyirira inoshanda paBDNF zvisina kunangana kuburikidza ne glutamate uye serotonin receptors. Ichi chidzidzo chinogona kuputsa pasi nekuti chinoratidza kuti mishonga yekudzvinyirira inotangisa kunanga kusunga kune BDNF receptors.

"Takaona kuti mishonga yekudzvinyirira inosimudzira chiratidzo cheBDNF nekusunga kune yavo TrkB receptor," akadaro Castrén mukuburitswa kwenhau. "Ichi chiratidzo chinodikanwa kune maseru nemaitiro emhedzisiro yeanodzvinyirira mumhando yedu yekuyedza. Mhedzisiro yeanodzvinyirira pa [neuronal] mapurasitiki haadi, nekudaro, anoda kuwedzerwa mumatanho eserotonin kana kuvharirwa kwevanogamuchira glutamate, sekufunga kwambofunga."

"Ongororo dzapamberi dzakaratidza kuti mukurapa kweSSRI, zvinodhaka zvinosvika padanho rekukwirisa huropi hunodiwa kuti usunge kune iyo TrkB receptor, nepo mukati mekubaya ketamine uye esketamine semushonga wemhino [kureva., Spravato] inosvika padanho rinodiwa rekusunga nekukurumidza, nyaya yemaminitsi, "Castrén akawedzera. "Musiyano mukutanga kwezviito zveSSRIs uye ketamine zvinogona kukonzerwa nekugona kwavo kwakasiyana kwekusvika muuropi mukumanikidza kunodiwa kusunga neTrocB receptors."

Molecular modelling inoitwa neIlpo Vattulainen's Dhipatimendi reFizikiki boka rekutsvagisa sechikamu chechidzidzo ichi chakaratidza "nzvimbo inosunga mishonga yekudzvinyirira mudunhu rekutapurirana reTrkB" uye "yakaratidza kuti chimiro cheTrkB chine hanya necholesterol yevasungwa yesero membrane . " Kugadzira shanduko yeTrkB antidepressant-inosunga motif zvese in vitro uye mu vivo "kukanganisika kwema cellular, hunhu, uye mapurasitiki-anokurudzira mhinduro kune anodzvinyirira."

Matatu-akanangiswa mabara kubva kuichi chidzidzo:

• Anoverengeka antidepressants, anosanganisira SSRIs uye ketamine, anosunga zvakananga kuTrkB.
• Antidepressant inosunga kuTrkB inobatsira BDNF chiito uye inosimudzira neuronal plasticity.
• Pfungwa inoshanduka muTrkB transmembrane dunhu inovhara mhedzisiro yemishonga inodzvinyirira.

Kunyangwe mishonga yekudzvinyirira senge fluoxetine (Prozac) uye sertraline (Zoloft) yakanzi "inosarudza serotonin reuptake inhibitors" nguva pfupi mushure mekubvumidzwa kwavo neDAA mukunopera kwema1980, kutanga kwema90s, muviri uri kukura weuchapupu hwezana ramakore rechi21 hunoratidza kuti izvi zvinodhaka shanda chete nekuwedzera mazinga eserotonin muuropi; zvakaoma kupfuura izvozvo. Kubva pane kuunganidza humbowo, mumwe anogona kufungidzira kuti iyo SSRI zita remanyorerwo rinokundikana kunyatsotsanangura mashandiro anoita aya antidepressants uye anogona kunge asiri iwo mazita.

SSRIs Inokosha Inoverengwa

Chikumbiro chezvePfungwa Dzakakwana Psychiatry