Hyoscyamine

Basic Info

Common NameHyoscyamine(F04807)
2D Structure
Description

Hyoscyamine is a chemical compound, a tropane alkaloid it is the levo-isomer to atropine. It is a secondary metabolite of some plants, particularly henbane (Hyoscamus niger.)
Hyoscyamine is used to provide symptomatic relief to various gastrointestinal disorders including spasms, peptic ulcers, irritable bowel syndrome, pancreatitis, colic and cystitis. It has also been used to relieve some heart problems, control some of the symptoms of Parkinson's disease, as well as for control of respiratory secretions in end of life care.

FRCD IDF04807
CAS Number101-31-5
PubChem CID64692
FormulaC17H23NO3
IUPAC Name

(8-methyl-8-azabicyclo[3.2.1]octan-3-yl) (2S)-3-hydroxy-2-phenylpropanoate

InChI Key

RKUNBYITZUJHSG-LGGPCSOHSA-N

InChI

InChI=1S/C17H23NO3/c1-18-13-7-8-14(18)10-15(9-13)21-17(20)16(11-19)12-5-3-2-4-6-12/h2-6,13-16,19H,7-11H2,1H3/t13?,14?,15?,16-/m1/s1

Canonical SMILES

CN1C2CCC1CC(C2)OC(=O)C(CO)C3=CC=CC=C3

Isomeric SMILES

CN1C2CCC1CC(C2)OC(=O)[C@H](CO)C3=CC=CC=C3

WikipediaHyoscyamine
Synonyms
        
            Cystospaz
        
            hyoscyamine
        
            L-Hyoscyamine
        
            Levsin
        
            Daturine
        
            l-Atropine
        
            1-Hyoscyamine
        
            Hyoscyamine (Daturine)
        
            (S)-Atropine
        
            Levbid
Classifies
                

                  
                    Plant Toxin
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassAlkaloids and derivatives
ClassTropane alkaloids
SubclassNot available
Intermediate Tree NodesNot available
Direct ParentTropane alkaloids
Alternative Parents
Molecular FrameworkAromatic heteropolycyclic compounds
SubstituentsTropane alkaloid - Beta-hydroxy acid - Monocyclic benzene moiety - Hydroxy acid - Piperidine - Benzenoid - N-alkylpyrrolidine - Pyrrolidine - Amino acid or derivatives - Carboxylic acid ester - Tertiary aliphatic amine - Tertiary amine - Carboxylic acid derivative - Monocarboxylic acid or derivatives - Azacycle - Organoheterocyclic compound - Organonitrogen compound - Amine - Hydrocarbon derivative - Organic oxide - Alcohol - Carbonyl group - Organopnictogen compound - Organic oxygen compound - Organooxygen compound - Organic nitrogen compound - Primary alcohol - Aromatic heteropolycyclic compound
DescriptionThis compound belongs to the class of organic compounds known as tropane alkaloids. These are organic compounds containing the nitrogenous bicyclic alkaloid parent N-Methyl-8-azabicyclo[3.2.1]octane.

Properties

Property NameProperty Value
Molecular Weight289.375
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count4
Rotatable Bond Count5
Complexity353
Monoisotopic Mass289.168
Exact Mass289.168
XLogP1.8
Formal Charge0
Heavy Atom Count21
Defined Atom Stereocenter Count1
Undefined Atom Stereocenter Count2
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9569
Human Intestinal AbsorptionHIA+0.9286
Caco-2 PermeabilityCaco2+0.8866
P-glycoprotein SubstrateSubstrate0.5000
P-glycoprotein InhibitorNon-inhibitor0.6542
Non-inhibitor0.8595
Renal Organic Cation TransporterInhibitor0.7956
Distribution
Subcellular localizationLysosome0.4825
Metabolism
CYP450 2C9 SubstrateNon-substrate0.7041
CYP450 2D6 SubstrateNon-substrate0.6838
CYP450 3A4 SubstrateSubstrate0.5496
CYP450 1A2 InhibitorNon-inhibitor0.9045
CYP450 2C9 InhibitorNon-inhibitor0.9275
CYP450 2D6 InhibitorNon-inhibitor0.9231
CYP450 2C19 InhibitorNon-inhibitor0.9285
CYP450 3A4 InhibitorNon-inhibitor0.9500
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9113
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.8354
Inhibitor0.5378
AMES ToxicityNon AMES toxic0.7742
CarcinogensNon-carcinogens0.9631
Fish ToxicityHigh FHMT0.8274
Tetrahymena Pyriformis ToxicityHigh TPT0.9314
Honey Bee ToxicityLow HBT0.5891
BiodegradationReady biodegradable0.5527
Acute Oral ToxicityIII0.7806
Carcinogenicity (Three-class)Non-required0.6945
Model Value Unit
Absorption
Aqueous solubility-1.8475LogS
Caco-2 Permeability1.1717LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.7305LD50, mol/kg
Fish Toxicity1.0113pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.7143pIGC50, ug/L

References

TitleJournalDatePubmed ID
Atropa belladonna neurotoxicity: Implications to neurological disorders.Food Chem Toxicol2018 Jun29653183
Isolation of atropine and scopolamine from plant material using liquid-liquid extraction and EXtrelut<sup>®</sup> columns.J Chromatogr B Analyt Technol Biomed Life Sci2017 Feb 127616063
Poisoned after Dinner: Dolma with Datura Stramonium.Turk J Emerg Med2015 Mar27437523
A case of pediatric age anticholinergic intoxication due to accidental Datura stramonium ingestion admitting with visual hallucination.Turk J Pediatr2014 May-Jun25341608
Intra- and inter-laboratory validation of a dipstick immunoassay for the detection of tropane alkaloids hyoscyamine and scopolamine in animal feed.Food Addit Contam Part A Chem Anal Control Expo Risk Assess201424823431
Accidental poisoning after ingestion of "aphrodisiac" berries: diagnosis by analytical toxicology.J Emerg Med2012 Jun21571482
Datura contamination of hay as the suspected cause of an extensive outbreak of impaction colic in horses.J S Afr Vet Assoc2005 Jun16108531
The influence of Datura ferox alkaloids on egg-laying hens.Vet Hum Toxicol1994 Apr8197722
Toxicity study of the main alkaloids of Datura ferox in broilers.Food Chem Toxicol1993 Nov8258413
The formation of 3 alpha- and 3 beta-acetoxytropanes by Datura stramonium transformed root cultures involves two acetyl-CoA-dependent acyltransferases.FEBS Lett1991 Nov 41959620
Growth and hyoscyamine production of 'hairy root' cultures of Datura stramonium in a modified stirred tank reactor.Appl Microbiol Biotechnol1990 May1366453

Targets

Target Details

Muscarinic acetylcholine receptor M1

General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
Mechanism of Action:
Hyoscyamine competes favorably with acetylcholine for binding at muscarinic receptors in the salivary, bronchial, and sweat glands as well as in the eye, heart, and gastrointestinal tract. The actions of hyoscyamine result in a reduction in salivary, bronchial, gastric and sweat gland secretions, mydriasis, cycloplegia, change in heart rate, contraction of the bladder detrusor muscle and of the gastrointestinal smooth muscle, and decreased gastrointestinal motility.
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
Target Details

Muscarinic acetylcholine receptor M2

General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
Mechanism of Action:
Hyoscyamine competes favorably with acetylcholine for binding at muscarinic receptors in the salivary, bronchial, and sweat glands as well as in the eye, heart, and gastrointestinal tract. The actions of hyoscyamine result in a reduction in salivary, bronchial, gastric and sweat gland secretions, mydriasis, cycloplegia, change in heart rate, contraction of the bladder detrusor muscle and of the gastrointestinal smooth muscle, and decreased gastrointestinal motility.
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
Target Details

Muscarinic acetylcholine receptor M3

General Function:
Receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
Mechanism of Action:
Hyoscyamine is an anticholinergic, specifically an antimuscarinic, and works by blocking the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the central nervous system.
References
  1. Wikipedia. Hyoscyamine. Last Updated 10 June 2009. : http://en.wikipedia.org/wiki/Hyoscyamine
Target Details

Muscarinic acetylcholine receptor M4

General Function:
Guanyl-nucleotide exchange factor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:
CHRM4
Uniprot ID:
P08173
Molecular Weight:
53048.65 Da
Mechanism of Action:
Hyoscyamine is an anticholinergic, specifically an antimuscarinic, and works by blocking the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the central nervous system.
References
  1. Wikipedia. Hyoscyamine. Last Updated 10 June 2009. : http://en.wikipedia.org/wiki/Hyoscyamine
Target Details

Muscarinic acetylcholine receptor M5

General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM5
Uniprot ID:
P08912
Molecular Weight:
60073.205 Da
Mechanism of Action:
Hyoscyamine is an anticholinergic, specifically an antimuscarinic, and works by blocking the action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and the central nervous system.
References
  1. Wikipedia. Hyoscyamine. Last Updated 10 June 2009. : http://en.wikipedia.org/wiki/Hyoscyamine