Skopolamin

Skopolamin
(IUPAC) ime
	(–)-(S)-3-hidroksi-2-fenilpropionska kiselina(1R,2R,4S,7S,9S)-9-metil-3-oksa-9-azatriciklo[3.3.1.02,4]non-7-il estar
Klinički podaci
Robne marke	Transdermskop
AHFS/Drugs.com	Monografija
Identifikatori
CAS broj	51-34-3
ATC kod	A04AD01 N05CM05, S01FA02
PubChem	5184
DrugBank	DB00747
ChemSpider	10194106
UNII	DL48G20X8X
KEGG	D00138
ChEBI	CHEBI:16794
ChEMBL	CHEMBL1201069
Hemijski podaci
Formula	C17H21NO4
Mol. masa	303,353 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C17H21NO4/c1-18-13-7-11(8-14(18)16-15(13)22-16)21-17(20)12(9-19)10-5-3-2-4-6-10/h2-6,11-16,19H,7-9H2,1H3/t11-,12-,13-,14+,15-,16+/m1/s1 ; Key: STECJAGHUSJQJN-FWXGHANASA-N
Farmakokinetički podaci
Bioraspoloživost	10 - 50%
Poluvreme eliminacije	4,5 časa
Farmakoinformacioni podaci
Trudnoća	C(US)
Pravni status	℞-only (SAD)
Način primene	transdermalno, okularno, oralno, supkutano, intravenozno, sublingvalno, rektalno, intramuskularno

Skopolamin (levo-duboisin, hioscin) je tropanski alkaloid lek koji deluje kao muskarinski antagonist. On je jedan od sekundarnih metabolita biljki iz Solanaceae familije (velebilja), kao što su crni zobnik, tatula i Andjelske trube (datura ili brugmansija), i žbunje (Duboisia).^[7]^[8] Mada se skopolamin ponekad prikazuje u javnosti kao štetan lek, njegove antiholinergijske osobine omogućavaju njegovu legitimnu medicinsku upotrebu u malim dozama, na primer za lečenje bolesti kretanja primenom transdermalnog flastera.^[9]

Etimologija

Skopolamin je dobio ime po biljnom rodu Scopolia^[8].^[10]

Biosinteza u biljkama

Biosinteza skopolamina počinje dekarboksilacijom L-ornitin do putrescina posredstvom ornitin dekarboksilaza (EC 4.1.1.17). Putrescin se metiliše do N-metilputrescina uz pomoć putrescin N-metiltransferaze (EC 2.1.1.53).^[11]

Putrescin oksidaza (EC 1.4.3.10) koja specifično prepoznaje metilisani purtrescin katalizuje deaminaciju ovog jedinjenja do 4-metilaminobutanala koji zatim podleže spontanom formiranju prstena do N-metil-pirolijumskog katjona. U sledećem koraku, pirolijumski katjon se kondenzuje sa acetoacetatnom kiselinom proizvodeći higrin. Higrin se dalje preuređuje do tropinona.^[11]

Tropinon reduktaza I (EC 1.1.1.206) konvertuje tropinon do tropina, koji se kondenzuje sa fenilacetatom izvedenim iz fenilalanina do litorina. Citohrom P450 klasifikovan kao Cyp80F1^[12] oksiduje i preuređuje litorin do hiosciaminskog aldehida. U finalnom koraku, hiosciamin podleže epoksidaciji koja je katalisana 6 beta-hidroksihiosciamin epoksidazom (EC 1.14.11.14) proizvodeći skopolamin.^[11]

Reference

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ ^6,0 ^6,1 Putcha, L.; Cintrón, N. M.; Tsui, J.; Vanderploeg, J. M.; Kramer, W. G. (1989). „Pharmacokinetics and Oral Bioavailability of Scopolamine in Normal Subjects”. Pharmacology Research 6 (6): 481–485. DOI:10.1023/A:1015916423156. PMID 2762223.
↑ Muranaka, T.; Ohkawa, H.; Yamada, Y. (1993). „Continuous Production of Scopolamine by a Culture of Duboisia leichhardtii Hairy Root Clone in a Bioreactor System”. Applied Microbiology and Biotechnology 40 (2–3): 219–223. DOI:10.1007/BF00170370. ^{[mrtav link]}
↑ ^8,0 ^8,1 The Chambers Dictionary. Allied Publishers. 1998. str. 788,1480. ISBN 9788186062258.
↑ White, P. F.; Tang, J.; Song, D. et al. (2007). „Transdermal Scopolamine: An Alternative to Ondansetron and Droperidol for the Prevention of Postoperative and Postdischarge Emetic Symptoms”. Anesthesia and Analgesia 104 (1): 92–96. DOI:10.1213/01.ane.0000250364.91567.72. PMID 17179250.
↑ Cattell, Henry Ware (1910). Lippincott's new medical dictionary: a vocabulary of the terms used in medicine, and the allied sciences, with their pronunciation, etymology, and signification, including much collateral information of a descriptive and encyclopedic character. Lippincott. str. 435. Pristupljeno 25. 2. 2012.
↑ ^11,0 ^11,1 ^11,2 Ziegler, J.; Facchini, P. J. (2008). „Alkaloid Biosynthesis: Metabolism and Trafficking”. Annual Review of Plant Biology 59 (1): 735–769. DOI:10.1146/annurev.arplant.59.032607.092730.
↑ Li, R.; Reed, D. W.; Liu, E.; Nowak, J.; Pelcher, L. E.; Page, J. E.; Covello, P. S. (2006). „Functional Genomic Analysis of Alkaloid Biosynthesis in Hyoscyamus niger Reveals a Cytochrome P450 Involved in Littorine Rearrangement”. Chemistry & Biology 13 (5): 513–520. DOI:10.1016/j.chembiol.2006.03.005.

Spoljašnje veze

	Portal Medicina
	Portal Hemija

Skopolamin

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.

[5] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[pmid2762223-6] 6,0 ^6,1 Putcha, L.; Cintrón, N. M.; Tsui, J.; Vanderploeg, J. M.; Kramer, W. G. (1989). „Pharmacokinetics and Oral Bioavailability of Scopolamine in Normal Subjects”. Pharmacology Research 6 (6): 481–485. DOI:10.1023/A:1015916423156. PMID 2762223.

[7] Muranaka, T.; Ohkawa, H.; Yamada, Y. (1993). „Continuous Production of Scopolamine by a Culture of Duboisia leichhardtii Hairy Root Clone in a Bioreactor System”. Applied Microbiology and Biotechnology 40 (2–3): 219–223. DOI:10.1007/BF00170370. ^{[mrtav link]}

[Chambers-8] 8,0 ^8,1 The Chambers Dictionary. Allied Publishers. 1998. str. 788,1480. ISBN 9788186062258.

[White-9] White, P. F.; Tang, J.; Song, D. et al. (2007). „Transdermal Scopolamine: An Alternative to Ondansetron and Droperidol for the Prevention of Postoperative and Postdischarge Emetic Symptoms”. Anesthesia and Analgesia 104 (1): 92–96. DOI:10.1213/01.ane.0000250364.91567.72. PMID 17179250.

[Cattell1910-10] Cattell, Henry Ware (1910). Lippincott's new medical dictionary: a vocabulary of the terms used in medicine, and the allied sciences, with their pronunciation, etymology, and signification, including much collateral information of a descriptive and encyclopedic character. Lippincott. str. 435. Pristupljeno 25. 2. 2012.

[Ziegler2008-11] 11,0 ^11,1 ^11,2 Ziegler, J.; Facchini, P. J. (2008). „Alkaloid Biosynthesis: Metabolism and Trafficking”. Annual Review of Plant Biology 59 (1): 735–769. DOI:10.1146/annurev.arplant.59.032607.092730.

[12] Li, R.; Reed, D. W.; Liu, E.; Nowak, J.; Pelcher, L. E.; Page, J. E.; Covello, P. S. (2006). „Functional Genomic Analysis of Alkaloid Biosynthesis in Hyoscyamus niger Reveals a Cytochrome P450 Involved in Littorine Rearrangement”. Chemistry & Biology 13 (5): 513–520. DOI:10.1016/j.chembiol.2006.03.005.

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