石房蛤毒素

石房蛤毒素
	IUPAC名; (3aS-(3a-α,4-α,10aR*))-2,6-Diamino-4-(((amino-carbonyl)oxy)methyl)-3a,4,8,9-tetrahydro-1H,10H-pyrrolo(1,2-c)purine-10,10-diol
識別
CAS號	35523-89-8
PubChem	37165
ChemSpider	34106
SMILES	O=C(OC[C@@H]2/N=C(/N)N3[C@]1(/N=C(\N[C@H]12)N)C(O)(O)CC3)N;
InChI	1/C10H17N7O4/c11-6-15-5-4(3-21-8(13)18)14-7(12)17-2-1-9(19,20)10(5,17)16-6/h4-5,19-20H,1-3H2,(H2,12,14)(H2,13,18)(H3,11,15,16)/t4-,5-,10-/m0/s1;
InChIKey	RPQXVSUAYFXFJA-HGRQIUPRBO
ChEBI	34970
KEGG	C13757
IUPHAR配體	2625
性質
化學式	C10H17N7O4
摩爾質量	299.29 g·mol−1
	若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

石房蛤毒素（Saxitoxin ，STX）是一種極強的神經毒素，是已知毒性最強的麻痹性貝類毒素（PST）。

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石房蛤毒素首次分離於簾蛤科的石房蛤體內，並由此得名。石房蛤毒素實際上是一些藻類和藍細菌所合成，通過食物鏈聚集到貝類體內。已知自然存在結構相似的神經毒素有超過50種，統稱為石房蛤毒素類，除了石房蛤毒素本身外，還有新石房蛤毒素（英語：neosaxitoxin）（NSTX）、膝溝藻毒素（英語：gonyautoxin）、脫氨甲酰基石房蛤毒素（英語：decarbamoylsaxitoxin）（dcSTX）等。

自然存在

自然界中，石房蛤毒素實際上是一些雙鞭毛蟲門下的藻類所合成的，如亞歷山大藻（英語：Alexandrium (genus)）、裸甲藻（英語：Gymnodinium），以及淡水中的藍細菌如魚腥藻屬、一些束絲藻屬、擬柱孢藻（英語：Cylindrospermopsis）、鞘絲藻（英語：Lyngbya）、浮絲藻屬等^[1]^[2]。被貝類進食後，累積在濾食器官（英語：Filter_feeder）中。此外，石房蛤毒素也曾在亞洲河魨的一些物種和巴西的羅非魚體內發現存在^[3]。產自美國的野生河魨，其體內石房蛤毒素濃度與產自南美^[4]、日本^[5]^[6]菲律賓和泰國的相似。河魨體內累積另一種著名的神經毒素，即河魨毒素。

有些被藻華所污染的貝類含有此毒素，誤食導致中毒。很多常見的經濟水產均可能受到污染，包括淡菜類、蛤蜊、生蚝和扇貝等。污染通常存在於溫帶海域，從美國西海岸到西歐、東亞、澳大利亞，新西蘭和南非等地海域都有可能。如果檢測到毒素存在，政府部門有時不得不採取捕撈禁令等措施以圖控制中毒事件。

結構與合成

石房蛤毒素的二鹽酸鹽是吸濕性的無定型固體。然而，其結構還是可以通過結晶衍生物的X射線晶體學確定。^[7]^[8]石房蛤毒素氧化生成高熒光性的嘌呤衍生物，被用於檢測分析。^[9]

石房蛤毒素已經得到全合成。^[10]^[11]^[12]

毒性

中毒機理

石房蛤毒素是一種選擇性的細胞膜鈉離子通道阻滯劑（英語：Sodium_channel_blocker）。^[13]它與神經元細胞膜上的鈉離子通道結合，抑制鈉離子通過細胞膜，從而阻止細胞電位的傳導，最終導致癱瘓。

劑量

對於豚鼠，肌肉注射的致死劑量約為5 μg/kg體重。小鼠的致死劑量與與給藥途徑有關為：腹膜內注射(LD50 = 10 μg/kg)，靜脈注射（LD50 = 3.4 μg/kg），口服（LD50 = 263 μg/kg）。人類經口服的LD50為5.7 μg/kg，換句話說，口服攝入0.57 mg的石房蛤毒素——一顆沙子大小的1/8，即可致命。注射的致死量約為0.6 μg/kg，是口服的十分之一。氣溶膠吸入的致死劑量約為5 mg·min/m³。石房蛤毒素可經開放傷口進入人體，劑量約為50 μg。^[14]

動物實驗顯示4-氨基吡啶有解毒作用，^[15]^[16]^[17]不過無人體實驗數據。

參考資料

[1]
Clark R. F.; Williams S. R.; Nordt S. P.; Manoguerra A. S. A review of selected seafood poisonings. Undersea Hyperb Med. 1999, 26 (3): 175–84 [2008-08-12]. PMID 10485519. （原始內容存檔於2011-08-11）.
[2]
Landsberg, Jan H. The Effects of Harmful Algal Blooms on Aquatic Organisms. Reviews in Fisheries Science. 2002, 10 (2): 113–390. doi:10.1080/20026491051695.
[3]
Galvão, J. A.; Oetterer, M.; Bittencourt-Oliveira Mdo, M. D. C.; Gouvêa-Barros, S.; Hiller, S.; Erler, K.; Luckas, B.; Pinto, E.; Kujbida, P. Saxitoxins accumulation by freshwater tilapia (Oreochromis niloticus) for human consumption. Toxicon. 2009, 54 (6): 891–894. PMID 19560484. doi:10.1016/j.toxicon.2009.06.021.
[4]
Lagos, N. S.; Onodera, H.; Zagatto, P. A.; Andrinolo, D. ́O.; Azevedo, S. M. F. Q.; Oshima, Y. The first evidence of paralytic shellfish toxins in the freshwater cyanobacterium Cylindrospermopsis raciborskii, isolated from Brazil. Toxicon. 1999, 37 (10): 1359–1373. PMID 10414862. doi:10.1016/S0041-0101(99)00080-X.
[5]
Sato, S.; Kodama, M.; Ogata, T.; Saitanu, K.; Furuya, M.; Hirayama, K.; Kakinuma, K. Saxitoxin as a toxic principle of a freshwater puffer, Tetraodon fangi, in Thailand. Toxicon. 1997, 35 (1): 137–140. PMID 9028016. doi:10.1016/S0041-0101(96)00003-7.
[6]
Deeds, J. R.; Landsberg, J. H.; Etheridge, S. M.; Pitcher, G. C.; Longan, S. W. Non-Traditional Vectors for Paralytic Shellfish Poisoning. Marine Drugs. 2008, 6 (2): 308–348. PMC 2525492 . PMID 18728730. doi:10.3390/md6020308.
[7]
Bordner J.; Thiessen W. E.; Bates H. A.; Rapoport H. The structure of a crystalline derivative of saxitoxin. The structure of saxitoxin. Journal of the American Chemical Society. 1975, 97 (21): 6008–12. doi:10.1021/ja00854a009.
[8]
Schantz E. J.; Ghazarossian V. E.; Schnoes H. K.; Strong F. M.; Springer J. P.; Pezzanite J. O.; Clardy J. The structure of saxitoxin. Journal of the American Chemical Society. 1975, 97 (5): 1238–1239. doi:10.1021/ja00838a045.
[9]
Bates H. A.; Kostriken R.; Rapoport H. A chemical assay for saxitoxin. Improvements and modifications. Journal of Agricultural and Food Chemistry. 1978, 26 (1): 252–4. doi:10.1021/jf60215a060.
[10]
Tanino H.; Nakata T.; Kaneko T.; Kishi Y. A stereospecific total synthesis of d,l-saxitoxin. Journal of the American Chemical Society. 1997, 99 (8): 2818–9. doi:10.1021/ja00450a079.
[11]
Bhonde V. R.; Looper R. E. A stereocontrolled synthesis of (+)-saxitoxin. Journal of the American Chemical Society. 2011, 133 (50): 20172–4. doi:10.1021/ja2098063.
[12]
Fleming J. J.; McReynolds M. D.; Du Bois J. (+)-Saxitoxin: a first and second generation stereoselective synthesis. Journal of the American Chemical Society. 2007, 129 (32): 9964–75. PMID 17658800. doi:10.1021/ja071501o.
[13]
Huot, R. I.; Armstrong, D. L.; Chanh, T. C. Protection against nerve toxicity by monoclonal antibodies to the sodium channel blocker tetrodotoxin. Journal of Clinical Investigation. June 1989, 83 (6): 1821–1826. PMC 303901 . PMID 2542373. doi:10.1172/JCI114087.
[14]
Patocka J; Stredav L. Price, Richard , 編. Brief Review of Natural Nonprotein Neurotoxins. ASA Newsletter (Applied Science and Analysis inc.). April 23, 2002, 02–2 (89): 16–23 [26 May 2012]. ISSN 1057-9419. （原始內容存檔於2013-01-04）.
[15]
Benton, B. J.; Keller, S. A.; Spriggs, D. L.; Capacio, B. R.; Chang, F. C. Recovery from the lethal effects of saxitoxin: A therapeutic window for 4-aminopyridine (4-AP). Toxicon. 1998, 36 (4): 571–588. PMID 9643470. doi:10.1016/s0041-0101(97)00158-x.
[16]
Chang, F. C.; Spriggs, D. L.; Benton, B. J.; Keller, S. A.; Capacio, B. R. 4-Aminopyridine reverses saxitoxin (STX)- and tetrodotoxin (TTX)-induced cardiorespiratory depression in chronically instrumented guinea pigs. Fundamental and Applied Toxicology. 1997, 38 (1): 75–88. PMID 9268607. doi:10.1006/faat.1997.2328.
[17]
Chen, H.; Lin, C.; Wang, T. Effects of 4-Aminopyridine on Saxitoxin Intoxication. Toxicology and Applied Pharmacology. 1996, 141 (1): 44–48. PMID 8917674. doi:10.1006/taap.1996.0258.

[uhm-1] [1]
Clark R. F.; Williams S. R.; Nordt S. P.; Manoguerra A. S. A review of selected seafood poisonings. Undersea Hyperb Med. 1999, 26 (3): 175–84 [2008-08-12]. PMID 10485519. （原始內容存檔於2011-08-11）.

[2] [2]
Landsberg, Jan H. The Effects of Harmful Algal Blooms on Aquatic Organisms. Reviews in Fisheries Science. 2002, 10 (2): 113–390. doi:10.1080/20026491051695.

[3] [3]
Galvão, J. A.; Oetterer, M.; Bittencourt-Oliveira Mdo, M. D. C.; Gouvêa-Barros, S.; Hiller, S.; Erler, K.; Luckas, B.; Pinto, E.; Kujbida, P. Saxitoxins accumulation by freshwater tilapia (Oreochromis niloticus) for human consumption. Toxicon. 2009, 54 (6): 891–894. PMID 19560484. doi:10.1016/j.toxicon.2009.06.021.

[4] [4]
Lagos, N. S.; Onodera, H.; Zagatto, P. A.; Andrinolo, D. ́O.; Azevedo, S. M. F. Q.; Oshima, Y. The first evidence of paralytic shellfish toxins in the freshwater cyanobacterium Cylindrospermopsis raciborskii, isolated from Brazil. Toxicon. 1999, 37 (10): 1359–1373. PMID 10414862. doi:10.1016/S0041-0101(99)00080-X.

[Sato,_S._1997-5] [5]
Sato, S.; Kodama, M.; Ogata, T.; Saitanu, K.; Furuya, M.; Hirayama, K.; Kakinuma, K. Saxitoxin as a toxic principle of a freshwater puffer, Tetraodon fangi, in Thailand. Toxicon. 1997, 35 (1): 137–140. PMID 9028016. doi:10.1016/S0041-0101(96)00003-7.

[6] [6]
Deeds, J. R.; Landsberg, J. H.; Etheridge, S. M.; Pitcher, G. C.; Longan, S. W. Non-Traditional Vectors for Paralytic Shellfish Poisoning. Marine Drugs. 2008, 6 (2): 308–348. PMC 2525492 . PMID 18728730. doi:10.3390/md6020308.

[7] [7]
Bordner J.; Thiessen W. E.; Bates H. A.; Rapoport H. The structure of a crystalline derivative of saxitoxin. The structure of saxitoxin. Journal of the American Chemical Society. 1975, 97 (21): 6008–12. doi:10.1021/ja00854a009.

[8] [8]
Schantz E. J.; Ghazarossian V. E.; Schnoes H. K.; Strong F. M.; Springer J. P.; Pezzanite J. O.; Clardy J. The structure of saxitoxin. Journal of the American Chemical Society. 1975, 97 (5): 1238–1239. doi:10.1021/ja00838a045.

[9] [9]
Bates H. A.; Kostriken R.; Rapoport H. A chemical assay for saxitoxin. Improvements and modifications. Journal of Agricultural and Food Chemistry. 1978, 26 (1): 252–4. doi:10.1021/jf60215a060.

[10] [10]
Tanino H.; Nakata T.; Kaneko T.; Kishi Y. A stereospecific total synthesis of d,l-saxitoxin. Journal of the American Chemical Society. 1997, 99 (8): 2818–9. doi:10.1021/ja00450a079.

[11] [11]
Bhonde V. R.; Looper R. E. A stereocontrolled synthesis of (+)-saxitoxin. Journal of the American Chemical Society. 2011, 133 (50): 20172–4. doi:10.1021/ja2098063.

[12] [12]
Fleming J. J.; McReynolds M. D.; Du Bois J. (+)-Saxitoxin: a first and second generation stereoselective synthesis. Journal of the American Chemical Society. 2007, 129 (32): 9964–75. PMID 17658800. doi:10.1021/ja071501o.

[pmid2542373-13] [13]
Huot, R. I.; Armstrong, D. L.; Chanh, T. C. Protection against nerve toxicity by monoclonal antibodies to the sodium channel blocker tetrodotoxin. Journal of Clinical Investigation. June 1989, 83 (6): 1821–1826. PMC 303901 . PMID 2542373. doi:10.1172/JCI114087.

[14] [14]
Patocka J; Stredav L. Price, Richard , 編. Brief Review of Natural Nonprotein Neurotoxins. ASA Newsletter (Applied Science and Analysis inc.). April 23, 2002, 02–2 (89): 16–23 [26 May 2012]. ISSN 1057-9419. （原始內容存檔於2013-01-04）.

[15] [15]
Benton, B. J.; Keller, S. A.; Spriggs, D. L.; Capacio, B. R.; Chang, F. C. Recovery from the lethal effects of saxitoxin: A therapeutic window for 4-aminopyridine (4-AP). Toxicon. 1998, 36 (4): 571–588. PMID 9643470. doi:10.1016/s0041-0101(97)00158-x.

[16] [16]
Chang, F. C.; Spriggs, D. L.; Benton, B. J.; Keller, S. A.; Capacio, B. R. 4-Aminopyridine reverses saxitoxin (STX)- and tetrodotoxin (TTX)-induced cardiorespiratory depression in chronically instrumented guinea pigs. Fundamental and Applied Toxicology. 1997, 38 (1): 75–88. PMID 9268607. doi:10.1006/faat.1997.2328.

[17] [17]
Chen, H.; Lin, C.; Wang, T. Effects of 4-Aminopyridine on Saxitoxin Intoxication. Toxicology and Applied Pharmacology. 1996, 141 (1): 44–48. PMID 8917674. doi:10.1006/taap.1996.0258.

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