Ziconotide peptide, cov khoom npe yog Prialt, uas yog ib qho khoom siv hluavtaws ω - conotoxin MVIIA thiab belongs rau intrathecal txhaj tshuaj analgesics. Nws ua kom muaj zog ua kom muaj zog los ntawm kev thaiv cov N- hom voltage-gated calcium channel (CaV2.2) hauv tus txha caj qaum dorsal horn, inhibiting qhov tso tawm ntawm qhov mob neurotransmitters. Pom zoo los ntawm US FDA thiab European Union hauv xyoo 2004, nws yog qhov tsim nyog rau cov neeg mob mob hnyav heev uas ua tsis tau lwm yam kev kho mob analgesic (xws li cov kab mob analgesics los yog intrathecal morphine), tshwj xeeb tshaj yog rau mob qog noj ntshav thiab mob neuropathic refractory.
Cov ntaub ntawv qhov chaw: Baidu Baike "Qikao Nuo Peptide"; WeChat pej xeem platform (Tencent) tau tshaj tawm tsab xov xwm "Chikunotide thiab Intrathecal txhaj tshuaj, muaj kev nyab xeeb thiab siv tau yooj yim los kho cov tshuaj kho mob, tsis muaj tshuaj tiv thaiv thiab tshuaj tiv thaiv"
Cov khoom tsim
Ziconotide Polyacetate COA
Cov ntaub ntawv tseem ceeb thiab lub hom phiaj ntawm kev ua
Ziconotide peptideyog peptide compound uas muaj 25 amino acids, nrog peb disulfide bonds nyob rau hauv lub molecule uas tsim ib tug ruaj khov "cysteine Knot" topology. Cov qauv no ua rau muaj txiaj ntsig zoo rau cov tshuaj lom neeg ruaj khov thiab kev sib haum xeeb ntawm peptide molecules, ua rau lawv tsis tshua muaj kev cuam tshuam rau protease degradation hauv vivo, thaum tseem muab ib qho tshwj xeeb spatial conformation rau lawv khi rau lub hom phiaj receptors. Nws cov ntsiab lus isoelectric (pI) yog kwv yees li 8.5-9.0, thiab vim muaj ntau yam amino acid residues (xws li lysine thiab arginine) hauv cov molecule, nws pom muaj zog alkalinity tag nrho. Nws muaj qee yam solubility hauv dej, feem ntau yog soluble hauv nruab nrab lossis tsis muaj zog acidic tsis daws teeb meem (xws li phosphate buffer tov, acetic acid tsis tov), tab sis muaj qis solubility hauv cov kuab tshuaj organic (xws li methanol, ethanol), thiab yuav luag insoluble hauv cov kuab tshuaj tsis muaj polar (xws li chloroform).
Cov ntaub ntawv qhov chaw: ChemicalBook hais txog tsab xov xwm "Ziconotide; 107452-89-1", luam tawm thaum Lub Kaum Hli 14, 2025.
Voltage gated calcium channels (VGCCs) yog ib qho tseem ceeb ntawm cov proteins uas tswj cov calcium ion thauj hauv cov hlwb. Raws li lawv qhov sib txawv sib txawv, lawv tuaj yeem muab faib ua ntau lub tsev neeg, ntawm cov CaV2.2 (N- hom voltage-gated calcium channels hauv cov ntaub so ntswg neural) ua lub luag haujlwm tseem ceeb hauv kev tso tawm neurotransmitter. Thaum lub cell membrane muaj peev xwm hloov pauv, CaV2.2 tau qhib tam sim ntawd, qhib lub rooj vag channel thiab tso cai rau cov neeg xa xov tooj cua calcium ions (Ca ² ⁺) kom nkag mus rau hauv daim nyias nyias los ntawm sab nraud, yog li txhawb kev tso tawm ntawm cov neurotransmitters thiab ua rau muaj kev cuam tshuam ntawm cov kev taw qhia hauv qab.
Thaum lub sij hawm kis tau tus mob teeb liab, nociceptive stimuli activate peripheral nociceptors, thiab cov teeb liab kis mus rau tus txha caj qaum los ntawm thawj afferent paj fibers (feem ntau me me myelinated A δ - thiab C-fibers). Hauv cov txheej txheem no, kev ua kom N- hom channel mediates tso tawm cov tshuaj neurotransmitters xws li tshuaj P (SP), calcitonin gene-txog peptide (CGRP), thiab glutamate, uas cuam tshuam rau qis qis neural activation thiab mob kev nkag siab. SP thiab CGRP tuaj yeem ua rau mob o thiab ua rau mob hnyav heev.
Cov ntaub ntawv Source:
Cov kab lus cuam tshuam ntawm Suav Academy ntawm Kev Tshawb Fawb, "Qhov no" Nees "Led the Way for Painkiller Research and Development", tau tshaj tawm thaum Lub Xya Hli 8, 2021.
Tsab xov xwm hais txog Zhihu Kem, "Structure of human Cav2.2 channel blocked by the painkiller ziconotide", tau luam tawm thaum Lub Xya Hli 7, 2021 (kab lus no qhia txog cov txiaj ntsig kev tshawb fawb ntawm Yan Ning pab neeg ntawm Princeton University luam tawm hauv Xwm, nthuav tawm lub hauv paus molecular ntawm ziconotide thaiv Cav2.2 qhov pores).
Lub tshuab thaiv N- hom calcium channels
Muaj peev xwm khi rau - κ B subunit ntawm N- hom calcium channels ntawm cov cell membrane. Raws li txoj cai, Chikanootide tau koom ua ke tag nrho los ntawm helices P1 thiab P2, uas txhawb kev xaiv cov ntxaij lim dej thiab lub voj voog extracellular (ECL) hauv - rov II, III, thiab IV. Txhawm rau hloov mus rau nws txoj kev khi, ECL ntawm rov ua dua III thiab ₂ δ -1 yuav tsum tau ua tib zoo tilted upwards. Kev tshawb fawb tau pom tias qhov ntxig ntawm Met12 residue ntawmziconotide peptiderau hauv lub hnab ntim hydrophobic tsim los ntawm Ile300, Phe302, thiab Leu305 hauv CaV2.2 nce nws txoj kev sib raug zoo rau lub hom phiaj, tab sis kuj tseem tuaj yeem cuam tshuam nrog qee qhov kev phiv tshuaj lom.
Cov ntaub ntawv qhov chaw: Zhihu Kab ntsig txog kab lus "Structure of Human Cav2.2 Channel Blocked by the Painkiller Ziconotide", luam tawm thaum Lub Xya Hli 7, 2021.
Thaum cov khoom khi rau N- hom calcium channels, nws ncaj qha thaiv cov ion channel pores, tiv thaiv cov transmembrane thauj calcium ions (Ca ² ⁺) mus rau hauv cov neurons. Raws li ib txwm muaj lub cev muaj zog, calcium ion influx yog qhov txuas tseem ceeb hauv kev tso tawm neurotransmitter. Piv txwv li, ntawm lub hauv paus afferent paj hlwb xaus, qhov nkag ntawm calcium ions kho los ntawm N- hom calcium channels txhawb kev tso tawm cov neurotransmitters xws li tshuaj P, CGRP, thiab glutamate. Thiab los ntawm kev thaiv cov txheej txheem no, kev tso tawm ntawm cov mob ntsig txog neurotransmitters raug txo. Tsiaj thwmsim tau pom tias tom qab kev tswj hwm, kev tso tawm ntawm excitatory neurotransmitters los ntawm thawj afferent hlab ntsha xaus yog txo qis, yog li exerting analgesic teebmeem.
Cov ntaub ntawv Source:
Cov lus hais txog ntawm Sohu lub vev xaib "Ziconotide; 107452-89-1; CKGKGAKCSRLMYDCCTGSCRSGKC_ Responsive_Dosy_Neuro" tau luam tawm thaum Lub Peb Hlis 16, 2025.
MCE (Shanghai Haoyuan Biopharmaceutical Technology Co., Ltd.) hais txog tsab xov xwm "Aconotide acetate", luam tawm nyob rau lub Kaum Ib Hlis 3, 2016 (txoj kev hais tias Aconotide acetate tuaj yeem txo cov calcium tam sim no los ntawm kev qhia ntawm 1B subunit hauv HEK hlwb, tsa-201 hlwb, thiab Xenopus laevis lux ocytes).
Qhov cuam tshuam ntawm cov txheej txheem ntawm kev ua haujlwm ntawm kev sib kis ntawm cov cim mob
(1) inhibit qhov tso tawm ntawm cov neurotransmitters los ntawm thawj cov paj hlwb xaus
Raws li tau hais ua ntej, tom qab kev ua kom lub peripheral nociceptors los ntawm nociceptive stimuli, cov teeb liab raug xa mus rau tus txha caj qaum los ntawm thawj cov paj hlwb afferent. Thaum lub sijhawm ua haujlwm no, kev ua haujlwm ntawm N- hom calcium channels ntawm thawj cov hlab ntsha xaus ua rau cov calcium ions nkag mus, uas ua rau muaj kev tso tawm cov neurotransmitters xws li tshuaj P, CGRP, thiab glutamate. Cov neurotransmitters no xa cov cim mob rau cov neurons nyob rau hauv lub dorsal horn ntawm tus txha caj qaum, uas yog txuas ntxiv mus rau lub hlwb kom tsim tau qhov mob.
Ziconotide peptide inhibits kev nkag mus ntawm calcium ions los ntawm thaiv N- hom calcium channels, yog li txo qhov tso tawm ntawm cov neurotransmitters. Piv txwv li, hauv kev sim autoimmune encephalomyelitis (EAE) nas qauv, tom qab kev tswj hwm, qib ntawm IL-1 thiab IL-23 nyob rau hauv lub hauv paus paj hlwb ntawm cov nas tau txo qis, thiab tus nqi ntawm IL-17 tsim nyob rau hauv tus po kuj txo. Qhov no qhia tau hais tias Ziconotide cuam tshuam rau kev tso tawm ntawm cov neurotransmitters thiab tsim cov khoom muaj feem cuam tshuam, yog li txo qhov mob.
Cov ntaub ntawv qhov chaw: MCE (Shanghai Haoyuan Biopharmaceutical Technology Co., Ltd.) hais txog tsab xov xwm "Zinc acetate", luam tawm rau lub Kaum Ib Hlis 3, 2016.
(2) Thaiv qhov kev sib kis ntawm qhov mob ntawm lub paj hlwb
Tus txha caj qaum yog qhov chaw nres tsheb tseem ceeb rau kev sib kis ntawm cov cim mob. Tom qab thawj cov paj hlwb xa cov cim mob mus rau dorsal horn ntawm tus txha caj qaum, lawv tau ua tiav los ntawm kev sib txuam neural network thiab tom qab ntawd xa mus rau lub hlwb los ntawm tus txha caj qaum neurons. Ua lub luag haujlwm ntawm tus txha caj qaum los ntawm inhibiting kev tso tawm ntawm cov neurotransmitters los ntawm thawj cov paj hlwb xaus, txo cov kev ua haujlwm ntawm tus txha caj qaum dorsal horn neurons thiab yog li thaiv kev sib kis ntawm qhov mob ntxiv mus rau lub hlwb.
Cov kev tshawb fawb soj ntsuam tau pom tias kev txhaj tshuaj intrathecal ntawm Ziconotide tuaj yeem txo qhov mob hauv cov neeg mob uas mob hnyav heev uas tsis teb lossis ua rau lwm yam kev kho mob xws li intrathecal morphine thiab cov tshuaj tua kab mob.
Piv txwv li, hauv qee qhov kev tshawb fawb soj ntsuam siv cov tshuaj titration qeeb, thawj koob tshuaj tsis pub tshaj 2.4 μ g / 24 teev (0.1 μ g / teev), thiab cov koob tshuaj tau nce 2-3 zaug hauv ib lub lis piam raws li tus neeg mob cov lus teb, nrog rau txhua qhov nce ntxiv tsis pub tshaj 2.4 μ g / 24 teev (0.1 μ g / teev). Txog hnub tim 21, qhov siab tshaj plaws tau pom zoo koob tshuaj yog 19.2 μ g / 24 teev (0.8 μ g / teev), thiab ntau tus neeg mob qhov mob tau txo qis, ua tsaug rau nws txoj kev tiv thaiv kab mob ntawm qhov mob.
Cov ntaub ntawv qhov chaw: Cov tshooj lus ntsig txog ntawm Sohu lub vev xaib hu ua "Ziconotide; 107452-89-1; CKGKGAKCSRLMYDCCTGSCRSGKC_ Teb, Dose, thiab Neurology", luam tawm thaum Lub Peb Hlis 16, 2025.
Ziconotide peptide, raws li ib qho tshwj xeeb N-hom voltage-gated calcium channel blocker, thaiv qhov nkag ntawm calcium ions los ntawm kev khi rau - κ B subunit ntawm N- hom calcium channels, inhibits kev tso tawm ntawm cov neurotransmitters los ntawm thawj afferent hlab ntsha xaus, thiab yog li thaiv kev sib kis ntawm lub paj hlwb, qhov mob tshwm sim. Nws cov txheej txheem tshwj xeeb ntawm kev nqis tes ua muab nws qhov zoo xws li tsis muaj kev tiv thaiv thiab kev tsis haum, muab kev nyab xeeb thiab kev kho mob zoo rau cov neeg mob uas mob hnyav, tshwj xeeb tshaj yog mob neuropathic thiab mob qog noj ntshav.
Cim npe nrov: Tuam Tshoj ziconotide peptide manufacturers, lwm tus neeg
