I-Cobenfy (KarXT): I-Antipical Antipsychotic yoNyango lweSchizophrenia

I-Cobenfy (ekwaziwa njenge-KarXT), indibaniselwano yamachiza xanomeline kunye ne-trospium chloride, ifundwe ukuba iyasebenza kunyango lwe-schizophrenia kwaye yamkelwe yi-FDA njenge-antipsychotic ngoSeptemba ka-2024.¹. Oku, nangona kunjalo, luhlobo olutsha ngokupheleleyo lonyango lwe-schizophrenia njengoko zonke iziyobisi zangaphambili zichasene ne-dopamine receptor (ebizwa ngokuba yi-antipsychotics eqhelekileyo), i-D2, kunye ne-serotonin receptor (ebizwa ngokuba yi-atypical antipsychotics), i-5-HT2A.²; kanti i-xanomeline i-acetylcholine muscarinic receptor agonist ye-M1 kunye ne-M4 subtypes³ kunye ne-trospium chloride yi-acetylcholine muscarinic receptor antagonist ye-M1, i-M2 kunye ne-M3 subtypes.⁴. Ngoko ke olu lunyango lwenoveli lwe-schizophrenia kwaye lucacisa ukuba kunokwenzeka ukuba kubekho ezinye ii-pharmacological agents ezingasetyenziswanga ezinokubandakanya ukujoliswa kwe-acetylcholine muscarinic receptors kunyango lwe-schizophrenia okanye i-psychosis ngokubanzi. 

kwengqondo sisigulo sengqondo esibonakala ngeempawu zengqondo ezifana nokukhohlisa, ukubona izinto ezingekhoyo kunye nokungabikho kwenkuthazo. Oku kucetywa ukuba kulawulwe ngokuyintloko ngenkqubo ye-dopaminergic kwaye kunokwenzeka ukuba ibandakanye inkqubo ye-serotonergic.⁵. Nangona kunjalo, i-acetylcholine muscarinic receptors ziyaziwa ukuba zisebenzisana kakhulu ne-dopamine neurons eziphembelela ukukhululwa kwazo kwe-dopamine kwi-neuronal synapses kunye nemiphumo ye-postsynaptic.⁶. Kungenxa yale ndlela yokuba i-antipsychotic yangaphambili, i-clozapine, echasene ne-serotonin kunye ne-dopamine receptors, kucingelwa ukuba ineprofayili yempembelelo engathandekiyo ngokungafaniyo nezinye ii-antipsychotics ngenxa yokuchasana kwayo ne-M1 i-acetylcholine receptors.⁵. 

Amalingo amathathu ekliniki alawulwa yi-placebo asebenzisa indibaniselwano yechiza njengonyango lwe-monotherapy kunyango lwezigulana ezine-schizophrenia eziye zaqaqanjelwa kakhulu yi-psychosis, kunye nolingo oluthatha iiveki ezi-5.⁷. Indibaniselwano yechiza igqwese kakhulu i-placebo ekunyangeni iimpawu ze-schizophrenic njengoko ilinganiswe yi-PANSS (Positive and Negative Syndrome Scale) kulingo lwezonyango, ngakumbi malunga neempawu ezingezizo ezinjengokunqongophala kwenkuthazo kunye nokusilela konxibelelwano, ebonisa ukuba lunyango olusebenzayo lwe-antipsychotic.⁷.  

Izibonelelo ezibonakaliswe ngokweklinikhi zokujolisa kwinkqubo ye-cholinergic yonyango lwe-schizophrenia kunye ne-psychosis ibonisa amandla onyango olutsha kwezi zigulo zengqondo ezinokuthi zibe yiprofayili yesiphumo esilungileyo xa kuthelekiswa ne-antipsychotics eqhelekileyo. 

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Ucaphulo  

1. Ukukhutshwa kweNdaba ze-FDA – i-FDA iVuma iChiza ngeNdlela eNtsha yokuSebenza kuNyango lweSchizophrenia. Ipapashwe nge-26 Septemba 2024. Ifumaneka e https://www.fda.gov/news-events/press-announcements/fda-approves-drug-new-mechanism-action-treatment-schizophrenia  

2. Chokhawala K, Stevens L. Amayeza e-Antipsychotic. [Ihlaziywe ngo-2023 Feb 26]. Ku: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Ifumaneka kwi: https://www.ncbi.nlm.nih.gov/books/NBK519503/ 

3. Xanomeline. Ngqo kwiNzululwazi. Ifumaneka e https://www.sciencedirect.com/topics/neuroscience/xanomeline  

4. Rovner, ES Trospium Chloride kuLawulo lwe-Overactive Bladder. Iziyobisi 64, 2433-2446 (2004). https://doi.org/10.2165/00003495-200464210-00005  

5. McCutcheon, uRobert A. et al. I-Schizophrenia, i-Dopamine kunye ne-Striatum: ukusuka kwi-Biology ukuya kwiimpawu. IiNdlela zeNeuroscience, uMqulu 42, ukukhutshwa kwe-3, 205 - 220. DOI: DOI: https://doi.org/10.1016/j.tins.2018.12.004  

6. Threlfell1 S. kunye neCragg SJ, 2011. I-Dopamine yokubonisa kwi-dorsal versus ventral striatum: indima eguquguqukayo ye-cholinergic interneurons. Ngaphambili. Inkqubo. Neurosci., 03 Matshi 2011. Umqulu 5 - 2011. DOI: https://doi.org/10.3389/fnsys.2011.00011  

7. Horan WP, okqhubekayo 2024. Ukusebenza kweKarXT kwiimpawu ezimbi kwi-schizophrenia enzima: Uhlalutyo lwe-post hoc lwedatha edibeneyo evela kwizilingo ze-3. Uphando lweSchizophrenia. Umqulu 274, kaDisemba 2024, iphepha 57-65. DOI: https://doi.org/10.1016/j.schres.2024.08.001  

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