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卡英酸：修订间差异

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{{medical}}
{{in use}}
{{chembox
{{Chembox
| Verifiedfields = changed
| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 402192845
| verifiedrevid = 477496607
| Reference = <ref>''Merck Index'', 11th Edition, '''5157'''</ref>
| ImageFile = Kainic acid.png
| ImageFile = Kainic acid.png
| ImageFile_Ref = {{chemboximage|correct|??}}
| ImageSize =
| ImageSize = 200px
| IUPACName = (2S,3S,4S)-3-(carboxymethyl)-4-prop-1-en-2-ylpyrrolidine-2-carboxylic acid
| ImageName = Stereo, skeletal formula of kainic acid
| OtherNames = 2-Carboxy-3-carboxymethyl-4-isopropenyl-pyrrolidine
| IUPACName = (2''S'',3''S'',4''S'')-3-(Carboxymethyl)-4-(prop-1-en-2-yl)pyrrolidine-2-carboxylic acid
| Section1 = {{Chembox Identifiers
| OtherNames = (3''S'',4''S'')-3-(Carboxymethyl)-4-prop-1-en-2-yl-<small>L</small>-proline; 2-Carboxy-3-carboxymethyl-4-isopropenyl-pyrrolidine{{Citation needed|date = May 2011}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
|Section1={{Chembox Identifiers
| CASNo = 487-79-6
| CASNo_Ref = {{cascite|correct|CAS}}
| PubChem = 10255
| ChemSpiderID = 9837
| ChemSpiderID = 9837
| UNII_Ref = {{fdacite|correct|FDA}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| UNII = SIV03811UC
| UNII = SIV03811UC
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| UNII_Ref = {{fdacite|correct|FDA}}
| ChEMBL = 275040
| KEGG = C12819
| KEGG_Ref = {{keggcite|changed|kegg}}
| InChI = 1/C10H15NO4/c1-5(2)7-4-11-9(10(14)15)6(7)3-8(12)13/h6-7,9,11H,1,3-4H2,2H3,(H,12,13)(H,14,15)/t6-,7+,9-/m0/s1
| MeSHName = Kainic+acid
| InChIKey = VLSMHEGGTFMBBZ-OOZYFLPDBV
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 31746
| StdInChI = 1S/C10H15NO4/c1-5(2)7-4-11-9(10(14)15)6(7)3-8(12)13/h6-7,9,11H,1,3-4H2,2H3,(H,12,13)(H,14,15)/t6-,7+,9-/m0/s1
| ChEMBL = 27527
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| StdInChIKey = VLSMHEGGTFMBBZ-OOZYFLPDSA-N
| Beilstein = 86660
| CASNo_Ref = {{cascite|correct|CAS}}
| SMILES = OC(=O)[C@H]1NC[C@H](C(C)=C)[C@@H]1CC(=O)O
| CASNo = 487-79-6
| StdInChI = 1S/C10H15NO4/c1-5(2)7-4-11-9(10(14)15)6(7)3-8(12)13/h6-7,9,11H,1,3-4H2,2H3,(H,12,13)(H,14,15)
| PubChem = 10255
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| SMILES = O=C(O)[C@H]1NC[C@H](\C(=C)C)[C@@H]1CC(=O)O
| StdInChIKey = VLSMHEGGTFMBBZ-UHFFFAOYSA-N
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
}}
|Section2={{Chembox Properties
| C=10 | H=15 | N=1 | O=4
| MeltingPtC = 215
| MeltingPt_notes = （然後分解）
| LogP = 0.635
| pKa = 2.031
| pKb = 11.966
}}
|Section3={{Chembox Structure
| CrystalStruct = Monoclinic
}}
}}
| Section2 = {{Chembox Properties
| Formula = C<SUB>10</SUB>H<SUB>15</SUB>NO<SUB>4</SUB>
| MolarMass = 213.23
| Appearance = Crystalline needles
| Density =
| MeltingPt = 215 °C (decomp.)
| BoilingPt =
| Solubility =
}}
| Section3 = {{Chembox Hazards
| MainHazards =
| FlashPt =
| Autoignition =
}}
}}
}}


'''卡英酸'''（{{lang-en|kainic acid}}），又稱'''紅藻酸'''、'''紅藻胺酸'''、'''海人酸'''，是一種類似[[麩胺酸]]（glutamic acid）的化合物，為[[神經傳遞]]很強的藥物，萃取自海底的[[藻類]]。
'''卡英酸'''（{{lang-en|kainic acid}}或{{lang|en|kainate}}），又稱'''紅藻酸'''、'''紅藻胺酸'''、'''海人酸'''或'''海人藻酸'''{{r|cqvip}}，是一種自然產生於[[海藻]]的[[有機酸]]，可萃取自海底的[[藻類]]。類似[[麩胺酸]]（glutamic acid）的化合物，卡英酸為[[神經傳遞]]很強的藥物，能夠刺激人體中央神經系統的主要[[神经递质]]的麩胺酸受體。


==發展歷史==
==醫學應用==
卡英酸最早於1953年由[[日本]]從[[海藻]]中分離出來
卡英酸最早由[[日本]]發現應用在孩童[[驅蟲藥]]，並且銷往[[東亞]]各國，早期[[台灣]]也是仰賴進口，甚至在公元1971年[[台灣]]景德製藥廠興建廠房大量生產海人酸，但在日本臨床上發現服用卡英酸治療[[寄生蟲]]的幼童都紛紛有[[癲癇]]的症狀，因此這個[[藥物]]馬上遭禁用。也因為這個醫療上的發現，使卡英酸發展成不同的應用方式，目前卡英酸應用在誘發[[癲癇]]。
<ref>{{cite journal | author = Moloney, Mark G. | title = Excitatory amino acids | journal = Natural Product Reports | year = 1998 | volume = 15 | issue = 2 | pages = 205–219 | doi = 10.1039/a815205y | pmid = 9586226}}</ref>，並應用在孩童[[驅蟲藥]]。卡英酸在日本的成功，讓他們把這種治療推廣至[[東亞]]各國。早期[[台灣]]也是仰賴進口，甚至在公元1971年[[台灣]]景德製藥廠興建廠房大量生產海人酸，但在日本臨床上發現服用卡英酸治療[[寄生蟲]]的幼童都紛紛有[[癲癇]]的症狀，因此這個[[藥物]]馬上遭禁用。也因為這個醫療上的發現，使卡英酸發展成不同的應用方式，目前卡英酸應用在誘發[[癲癇]]。
==Pharmacological activity==
Kainic acid is utilised in primary neuronal cell cultures<ref>{{cite journal|last1=Meade|first1=AJ|last2=Meloni|first2=BP|last3=Mastaglia|first3=FL|last4=Watt|first4=PM|last5=Knuckey|first5=NW|title=AP-1 inhibitory peptides attenuate in vitro cortical neuronal cell death induced by kainic acid.|journal=Brain Research|date=Nov 11, 2010|volume=1360|pages=8–16|pmid=20833150|doi=10.1016/j.brainres.2010.09.007}}</ref> and in the acute brain slice preparation<ref>{{cite book|last1=Craig|first1=Amanda|last2=Housley|first2=Gary|last3=Fath|first3=Thomas|title=Modeling excitotoxic ischaemic brain injury of cerebellar Purkinje neurons by intravital and in vitro multi-photon laser scanning microscopy|date=2014|publisher=Springer|isbn=978-1-4939-0380-1|pages=105–128}}</ref> to study the physiological effect of excitotoxicity and assess the neuroprotective capabilities of potential therapeutics.


Kainic acid is a potent <!-- [[central nervous system]] -->[[中樞神經系統]] excitant that is used in epilepsy research to induce seizures in experimental animals<ref>{{Cite book|title=A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy.|last=Barrow, Paul Anthony.|oclc=53634796}}</ref>, at a typical dose of 10–30&nbsp;mg/kg in mice. In addition to inducing seizures, kainic acid is excitotoxic and epileptogenic.<ref>{{cite book | author = Ben-Ari, Y | title = Kainate and Temporal Lobe Epilepsies: 3 decades of progress | booktitle =Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012. | url=https://www.ncbi.nlm.nih.gov/books/NBK98166/ |pmid = 22787646| year = 2012 | publisher = National Center for Biotechnology Information (US) }}</ref> Kainic acid induces seizures via activation of {{tsl|en|kainate receptor||kainate receptor}}s containing the {{tsl|en|GluK2||GluK2}} subunit and also through activation of AMPA receptors, for which it serves as a partial agonist.<ref>{{cite journal |vauthors=Fritsch B, Reis J, Gasior M, Kaminski RM, Rogawski MA |title=Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis |journal=Journal of Neuroscience |volume=34 |issue=17 |pages=5765–75 |date=April 2014 |pmid=24760837 |doi=10.1523/JNEUROSCI.5307-13.2014 |url=|pmc=3996208 }}</ref> Also, infusion with kainic acid in the hippocampus of animals results in major damage of pyramidal neurons and subsequent seizure activity. Supply shortages beginning in 2000 have caused the cost of kainic acid to rise significantly.
==實驗應用==
===相關文獻記載===
根據文獻指出（Schowb et al.﹐1980；Nitecka et al.﹐ 1984；Tremblay et al.﹐ 1984）發現在[[大鼠]]的[[腹腔]]或[[腦]]內注射卡英酸在[[海馬迴]]與[[杏仁核]]這兩個區域會產生[[癲癇]]的症狀，並且會產生神經興奮[[毒素]]。


===細胞實驗應用===
==應用==
* [[杜蟲藥]]（不建議）
在[[細胞]]實驗中則應用則常使用[[PC12细胞]]株來誘發[[癲癇]]。卡英酸在細胞實驗中，能誘導細胞產生模擬癲癇的狀態發生時的腦部神經過度活躍，並且產生ROS(reactive oxygen species)[[自由基]]釋放，造成神經細胞產生脂質過氧化物，會促使神經[[細胞]]的發炎反應，例如第二型環氧化酶COX-2、前列腺素E2、有絲蛋白活化激脢（MAPKs）、RhoA.....等分子生物發炎傳遞路徑。也會促使神經細胞PC12產生鈣離子的釋放並且造成細胞凋亡，是目前治療癲癇的藥物實驗中常運用來誘導的藥物。
* [[神经科学]]方面的研究
** neurodegenerative agent
** modeling of <!-- [[epilepsy]] -->[[癫痫]]<ref>{{Cite book|title=A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy.|last=Barrow, Paul Anthony.|oclc=53634796}}</ref>
** modeling of <!-- [[Alzheimer's disease]] -->[[阿茲海默症]]


==參看==
===動物發作等級===
* {{tsl|en|Dihydrokainic acid||Dihydrokainic acid}}
SD大鼠注射卡英酸後根據資料顯示(I. A, I.M, K. S, Y. R. Pentylenetetrazol-induced kindlingseizure attenuated by Ginkgo biloba extract (EGb 761) in mice. Prog NeuropsychopharmacolBiol Psychiatry 2006;30:1504–10.
* {{tsl|en|Domoic acid||Domoic acid}}
)有五個等級，以這五個等級做為誘導[[癲癇]]的症狀依據，許多治療癲癇的藥物也以這五個等地來進行觀察給予評分。
* [[Kainate receptor]]


==參考文獻==
*第一級 點頭
{{Reflist|2|refs=
*第二級 濕狗搖擺（wet dogshake ，形容大鼠會注射卡英酸後會呈現濕狗甩毛的動作）
<ref>{{cite journal
*第三級 前肢緩慢的節拍運動
|url=http://www.cqvip.com/qk/84220a/200919/32286893.html
*第四級 抽搐及後肢癱瘓
|author1=[[李建明]] |author2=[[雷德亮]] |year=2009
*第五級 全身抽搐及僵直的部分擴大
|title=KA海马注射对大鼠学习和记忆的影响及雷公藤甲素的保护作用
|journal=《[[现代生物医学进展]]》|issue=第19期 |language=zh-hans }}</ref>
}}


==参考==
==外部連結==
*[https://web.archive.org/web/20071028195503/http://www.bris.ac.uk/Depts/Synaptic/info/kainate/kainate_1.htm Kainate Receptors]
{{reflist}}


{{Glutamate receptor modulators}}
{{Glutamate metabolism and transport modulators}}
{{Authority control}}
{{Authority control}}

[[Category:氨基酸]]
[[Category:氨基酸]]
[[Category:吡咯烷]]
[[Category:吡咯烷]]
[[Category:惊厥剂]]
[[Category:惊厥剂]]
[[Category:海洋神经毒素]]
<!-- 沒有連結 -->[[Category:Kainate receptor agonists]]
[[Category:螯合配体]]
<!-- 沒有連結 -->[[Category:Toxic amino acids]]
[[Category:二羧酸]]
<!-- 沒有連結 -->[[Category:Excitotoxins]]
<!-- 沒有連結 -->[[Category:Isopropenyl compounds]]

2020年11月3日 (二) 07:25的版本

卡英酸
IUPAC名
(2S,3S,4S)-3-(Carboxymethyl)-4-(prop-1-en-2-yl)pyrrolidine-2-carboxylic acid
别名 (3S,4S)-3-(Carboxymethyl)-4-prop-1-en-2-yl-L-proline; 2-Carboxy-3-carboxymethyl-4-isopropenyl-pyrrolidine[來源請求]
识别
CAS号 487-79-6  checkY
PubChem 10255
ChemSpider 9837
SMILES
 
  • OC(=O)[C@H]1NC[C@H](C(C)=C)[C@@H]1CC(=O)O
Beilstein 86660
ChEBI 31746
KEGG C12819
MeSH Kainic+acid
性质
化学式 C10H15NO4
摩尔质量 213.23 g·mol−1
熔点 215 °C（488 K）
log P 0.635
pKa 2.031
pKb 11.966
结构
晶体结构 Monoclinic
若非注明，所有数据均出自标准状态（25 ℃，100 kPa）下。

卡英酸（英語：kainic acid或kainate），又稱紅藻酸、紅藻胺酸、海人酸或海人藻酸[1]，是一種自然產生於海藻的有機酸，可萃取自海底的藻類。類似麩胺酸（glutamic acid）的化合物，卡英酸為神經傳遞很強的藥物，能夠刺激人體中央神經系統的主要神经递质的麩胺酸受體。

醫學應用

卡英酸最早於1953年由日本從海藻中分離出來 [2]，並應用在孩童驅蟲藥。卡英酸在日本的成功，讓他們把這種治療推廣至東亞各國。早期台灣也是仰賴進口，甚至在公元1971年台灣景德製藥廠興建廠房大量生產海人酸，但在日本臨床上發現服用卡英酸治療寄生蟲的幼童都紛紛有癲癇的症狀，因此這個藥物馬上遭禁用。也因為這個醫療上的發現，使卡英酸發展成不同的應用方式，目前卡英酸應用在誘發癲癇。

Pharmacological activity

Kainic acid is utilised in primary neuronal cell cultures[3] and in the acute brain slice preparation[4] to study the physiological effect of excitotoxicity and assess the neuroprotective capabilities of potential therapeutics.

Kainic acid is a potent 中樞神經系統 excitant that is used in epilepsy research to induce seizures in experimental animals[5], at a typical dose of 10–30 mg/kg in mice. In addition to inducing seizures, kainic acid is excitotoxic and epileptogenic.[6] Kainic acid induces seizures via activation of kainate receptor（英语：kainate receptor）s containing the GluK2（英语：GluK2） subunit and also through activation of AMPA receptors, for which it serves as a partial agonist.[7] Also, infusion with kainic acid in the hippocampus of animals results in major damage of pyramidal neurons and subsequent seizure activity. Supply shortages beginning in 2000 have caused the cost of kainic acid to rise significantly.

應用

參看

參考文獻

  1. ^ 引用错误：没有为名为cqvip的参考文献提供内容
  2. ^ Moloney, Mark G. Excitatory amino acids. Natural Product Reports. 1998, 15 (2): 205–219. PMID 9586226. doi:10.1039/a815205y. 
  3. ^ Meade, AJ; Meloni, BP; Mastaglia, FL; Watt, PM; Knuckey, NW. AP-1 inhibitory peptides attenuate in vitro cortical neuronal cell death induced by kainic acid.. Brain Research. Nov 11, 2010, 1360: 8–16. PMID 20833150. doi:10.1016/j.brainres.2010.09.007. 
  4. ^ Craig, Amanda; Housley, Gary; Fath, Thomas. Modeling excitotoxic ischaemic brain injury of cerebellar Purkinje neurons by intravital and in vitro multi-photon laser scanning microscopy. Springer. 2014: 105–128. ISBN 978-1-4939-0380-1. 
  5. ^ Barrow, Paul Anthony. A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy.. OCLC 53634796. 
  6. ^ Ben-Ari, Y. Kainate and Temporal Lobe Epilepsies: 3 decades of progress. National Center for Biotechnology Information (US). 2012. PMID 22787646.  |booktitle=被忽略 (帮助)
  7. ^ Fritsch B, Reis J, Gasior M, Kaminski RM, Rogawski MA. Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis. Journal of Neuroscience. April 2014, 34 (17): 5765–75. PMC 3996208 可免费查阅. PMID 24760837. doi:10.1523/JNEUROSCI.5307-13.2014. 
  8. ^ Barrow, Paul Anthony. A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy.. OCLC 53634796. 
引用错误：<references>中定义的<ref>没有给出name属性

外部連結

Template:Glutamate receptor modulators Template:Glutamate metabolism and transport modulators

规范控制数据库：各地 編輯維基數據鏈接
取自“https://zh.wikipedia.org/w/index.php?title=卡英酸&oldid=62647808”