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Scopolamine: a journey from the field to clinics

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Abstract

Tropane alkaloids are present in many different plants of the Solanaceae family and widely known for their anticholinergic properties. Among them, most valued and increasingly demanded is scopolamine, also known under the name of hyoscine, which is used as pharmaceutical active substance in the treatment of postoperative nausea and vomiting, motion sickness and gastrointestinal, renal and biliary spasms for instance. It naturally occurs in various plant genera, e.g. Anisodus, Anthocercis, Atropa, Brugmansia, Datura, Duboisia, Hyoscyamus, Mandragora and Scopolia and the purified substance has a long history of use dating back to the nineteenth century. Until today, the supply in scopolamine is mainly covered by large scale field plant cultivation of hybrids between Duboisia myoporoides and Duboisia leichhardtii. Biotechnological approaches optimising the alkaloid biosynthesis, for example the use of callus cultures or genetically transformed hairy root cultures, are not competitive by now. The aim of this review is to give a comprehensive overview regarding the current knowledge on botanical origin, pharmacology, biosynthesis as well as agricultural and biotechnological production of scopolamine.

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Abbreviations

ArgDC:

Arginine decarboxylase

CNS:

Central nervous system

Cyp80F:

Cytochrome P450 80F1

E. coli :

Escherichia coli

GST-tag:

Gluthation-S-transferase-tag

HIS-tag:

Polyhistidine-tag

H6H/h6h :

Hyoscyamine 6β-hydroxylase (enzyme/gene)

mAChR:

Muscarinic acetylcholine receptors

MPO:

N-methylputrescine oxidase

OrnDC:

Ornithine decarboxylase

PMT/pmt :

Putrescine N-methyltransferase (enzyme/gene)

S. cerevisiae :

Saccharomyces cerevisiae

SAM:

S-adenosylmethionine

TR-1/tr-1 :

Tropinone-reductase I (enzyme/gene)

TR-2/tr-2 :

Tropinone-reductase I (enzyme/gene)

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Acknowledgments

The research from the DISCO project leading to these results has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement 613513. This work is furthermore supported financially by Boehringer Ingelheim Pharma GmbH & Co. KG.. The authors are grateful to Andreas Rothauer for literature supply and proof reading of the manuscript.

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Ullrich, S.F., Hagels, H. & Kayser, O. Scopolamine: a journey from the field to clinics. Phytochem Rev 16, 333–353 (2017). https://doi.org/10.1007/s11101-016-9477-x

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