降菸鹼

降菸鹼
	IUPAC名; 3-[(2S)-2-Pyrrolidinyl]pyridine
別名	去甲菸鹼、原菸鹼
識別
CAS號	494-97-3
PubChem	91462
ChemSpider	82588
SMILES	n1cccc(c1)[C@H]2NCCC2;
InChI	1/C9H12N2/c1-3-8(7-10-5-1)9-4-2-6-11-9/h1,3,5,7,9,11H,2,4,6H2/t9-/m0/s1;
InChIKey	MYKUKUCHPMASKF-VIFPVBQEBM
性質
化學式	C9H12N2
摩爾質量	148.2 g·mol−1
	若非註明，所有數據均出自標準狀態（25 ℃，100 kPa）下。

降菸鹼是存在於菸草等植物的生物鹼，化學式為C₉H₁₂N₂。^[1]它的結構與菸鹼相似，但少了一個甲基，因此又稱去甲菸鹼。

降菸鹼在醃製、加工菸草時會變為1類致癌物^[2]N-亞硝基降菸鹼。^[3]降菸鹼與口水反應也會產生N-亞硝基降菸鹼。^[4]

合成

降菸鹼可通過用氧化銀將菸鹼去甲基化而成。^[5]

\mathrm {\xrightarrow[{H_{2}O}]{Ag_{2}O}}

它也可由麥斯明（英語：myosmine）的催化氫化^[6]或被硼氫化鈉還原產生。^[7]

\mathrm {\xrightarrow[{H_{2}}]{Pd/C}}

藥學作用

降菸鹼與菸鹼型乙醯膽鹼受體的親和力高^[8]，會以此抑制大鼠紋狀體的多巴胺轉運體，釋放多巴胺。^[9]^[10]^[11]

參考資料

^ Laszlo C, Kaminski K, Guan H, Fatarova M, Wei J, Bergounioux A, Schlage WK, Schorderet-Weber S, Guy PA, Ivanov NV, Lamottke K, Hoeng J. Fractionation and Extraction Optimization of Potentially Valuable Compounds and Their Profiling in Six Varieties of Two Nicotiana Species. Molecules. November 2022, 27 (22): 8105. PMC 9694777 . PMID 36432206. doi:10.3390/molecules27228105 .
^ List of Classifications – IARC Monographs on the Identification of Carcinogenic Hazards to Humans. monographs.iarc.fr. [2020-07-22]. （原始內容存檔於2020-05-20）.
^ Siminszky, B. Conversion of nicotine to nornicotine in Nicotiana tabacum is mediated by CYP82E4, a cytochrome P450 monooxygenase. Proceedings of the National Academy of Sciences. 2005, 102 (41): 14919–24. PMC 1253577 . PMID 16192354. doi:10.1073/pnas.0506581102 .
^ Knezevich A, Muzic J, Hatsukami DK, Hecht SS, Stepanov I. Nornicotine nitrosation in saliva and its relation to endogenous synthesis of N'-nitrosonornicotine in humans. Nicotine & Tobacco Research. February 2013, 15 (2): 591–5. PMC 3611998 . PMID 22923602. doi:10.1093/ntr/nts172.
^ Spaeth. Über dasd-Nor-nicotin. Chem. Ber. 1936, 69 (2): 250–251. doi:10.1002/cber.19360690207.
^ Haines. Chemical Reactivity of Myosmine. J. Am. Chem. Soc. 1945, 67 (8): 1258–1260. doi:10.1021/ja01224a011.
^ Dickerson, TJ; Janda, KD. Aqueous aldol catalysis by a nicotine metabolite. J. Am. Chem. Soc. 2002, 124 (13): 3220–1. PMID 11916401. doi:10.1021/ja017774f. .
^ Papke RL, Dwoskin LP, Crooks PA. The pharmacological activity of icotine and nornicotine on nAChRs subtypes: relevance to nicotine dependence and drug discovery. Journal of Neurochemistry. April 2007, 101 (1): 160–7. PMID 17241116. doi:10.1111/j.1471-4159.2006.04355.x .
^ Middleton LS, Crooks PA, Wedlund PJ, Cass WA, Dwoskin LP. Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation. Synapse. March 2007, 61 (3): 157–65. PMID 17146768. S2CID 35071082. doi:10.1002/syn.20351.
^ Dwoskin LP, Teng LH, Crooks PA. Nornicotine, a nicotine metabolite and tobacco alkaloid: desensitization of nicotinic receptor-stimulated dopamine release from rat striatum. European Journal of Pharmacology. September 2001, 428 (1): 69–79. PMID 11779039. doi:10.1016/s0014-2999(01)01283-3.
^ Dwoskin LP, Buxton ST, Jewell AL, Crooks PA. S(-)-nornicotine increases dopamine release in a calcium-dependent manner from superfused rat striatal slices. Journal of Neurochemistry. June 1993, 60 (6): 2167–74. PMID 8492124. S2CID 25622404. doi:10.1111/j.1471-4159.1993.tb03502.x.

[1] Laszlo C, Kaminski K, Guan H, Fatarova M, Wei J, Bergounioux A, Schlage WK, Schorderet-Weber S, Guy PA, Ivanov NV, Lamottke K, Hoeng J. Fractionation and Extraction Optimization of Potentially Valuable Compounds and Their Profiling in Six Varieties of Two Nicotiana Species. Molecules. November 2022, 27 (22): 8105. PMC 9694777 . PMID 36432206. doi:10.3390/molecules27228105 .

[:2-2] List of Classifications – IARC Monographs on the Identification of Carcinogenic Hazards to Humans. monographs.iarc.fr. [2020-07-22]. （原始內容存檔於2020-05-20）.

[3] Siminszky, B. Conversion of nicotine to nornicotine in Nicotiana tabacum is mediated by CYP82E4, a cytochrome P450 monooxygenase. Proceedings of the National Academy of Sciences. 2005, 102 (41): 14919–24. PMC 1253577 . PMID 16192354. doi:10.1073/pnas.0506581102 .

[:1-4] Knezevich A, Muzic J, Hatsukami DK, Hecht SS, Stepanov I. Nornicotine nitrosation in saliva and its relation to endogenous synthesis of N'-nitrosonornicotine in humans. Nicotine & Tobacco Research. February 2013, 15 (2): 591–5. PMC 3611998 . PMID 22923602. doi:10.1093/ntr/nts172.

[späth-5] Spaeth. Über dasd-Nor-nicotin. Chem. Ber. 1936, 69 (2): 250–251. doi:10.1002/cber.19360690207.

[6] Haines. Chemical Reactivity of Myosmine. J. Am. Chem. Soc. 1945, 67 (8): 1258–1260. doi:10.1021/ja01224a011.

[7] Dickerson, TJ; Janda, KD. Aqueous aldol catalysis by a nicotine metabolite. J. Am. Chem. Soc. 2002, 124 (13): 3220–1. PMID 11916401. doi:10.1021/ja017774f. .

[pmid17241116-8] Papke RL, Dwoskin LP, Crooks PA. The pharmacological activity of icotine and nornicotine on nAChRs subtypes: relevance to nicotine dependence and drug discovery. Journal of Neurochemistry. April 2007, 101 (1): 160–7. PMID 17241116. doi:10.1111/j.1471-4159.2006.04355.x .

[pmid17146768-9] Middleton LS, Crooks PA, Wedlund PJ, Cass WA, Dwoskin LP. Nornicotine inhibition of dopamine transporter function in striatum via nicotinic receptor activation. Synapse. March 2007, 61 (3): 157–65. PMID 17146768. S2CID 35071082. doi:10.1002/syn.20351.

[pmid11779039-10] Dwoskin LP, Teng LH, Crooks PA. Nornicotine, a nicotine metabolite and tobacco alkaloid: desensitization of nicotinic receptor-stimulated dopamine release from rat striatum. European Journal of Pharmacology. September 2001, 428 (1): 69–79. PMID 11779039. doi:10.1016/s0014-2999(01)01283-3.

[pmid8492124-11] Dwoskin LP, Buxton ST, Jewell AL, Crooks PA. S(-)-nornicotine increases dopamine release in a calcium-dependent manner from superfused rat striatal slices. Journal of Neurochemistry. June 1993, 60 (6): 2167–74. PMID 8492124. S2CID 25622404. doi:10.1111/j.1471-4159.1993.tb03502.x.

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