T3DB: Slaframine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (5)XML

Targets (5)

Record Information

Version

2.0

Creation Date

2010-05-27 14:58:19 UTC

Update Date

2014-12-24 20:26:32 UTC

Accession Number

T3D3775

Identification

Common Name

Slaframine

Class

Small Molecule

Description

Slaframine is a mycotoxin produced by the fungus Rizoctonia leguminicola. It is a parasympathomimetic compound and causes increased exocrine function, especially salivation. Along with swainsonine, the other biologially active compound of R. leguminicola, it is known to cause a condition called "slobbers syndrome" in livestock that has ingested contaminated feed. (1, 2)

Compound Type

Amine
Ester
Ether
Fungal Toxin
Mycotoxin
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(1S,6S,8aS)-1-Acetoxy-6-aminooctahydroindolizine
(1S-(1alpha,6alpha,8abeta))-6-Aminooctahydro-1-indolizinol, acetate (ester)

Chemical Formula

C₁₀H₁₈N₂O₂

Average Molecular Mass

198.262 g/mol

Monoisotopic Mass

198.137 g/mol

CAS Registry Number

20084-93-9

IUPAC Name

6-amino-octahydroindolizin-1-yl acetate

Traditional Name

slaframine

SMILES

CC(=O)OC1CCN2CC(N)CCC12

InChI Identifier

InChI=1S/C10H18N2O2/c1-7(13)14-10-4-5-12-6-8(11)2-3-9(10)12/h8-10H,2-6,11H2,1H3

InChI Key

InChIKey=YYIUHLPAZILPSG-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as indolizidines. These are polycyclic compounds containing an indolizidine, which is a bicyclic heterocycle containing a saturated six-member ring fused to a saturated five-member ring, one of the bridging atoms being nitrogen.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Indolizidines

Sub Class

Not Available

Direct Parent

Indolizidines

Alternative Parents

Substituents

Indolizidine
3-aminopiperidine
Piperidine
N-alkylpyrrolidine
Pyrrolidine
Amino acid or derivatives
Carboxylic acid ester
Tertiary amine
Tertiary aliphatic amine
Monocarboxylic acid or derivatives
Carboxylic acid derivative
Azacycle
Organic oxide
Primary amine
Organopnictogen compound
Organooxygen compound
Organonitrogen compound
Primary aliphatic amine
Organic oxygen compound
Amine
Carbonyl group
Organic nitrogen compound
Hydrocarbon derivative
Aliphatic heteropolycyclic compound

Molecular Framework

Aliphatic heteropolycyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	250 g/L	ALOGPS
logP	-0.07	ALOGPS
logP	-0.38	ChemAxon
logS	0.1	ALOGPS
pKa (Strongest Basic)	9.82	ChemAxon
Physiological Charge	2	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	55.56 Å²	ChemAxon
Rotatable Bond Count	2	ChemAxon
Refractivity	52.83 m³·mol⁻¹	ChemAxon
Polarizability	21.7 Å³	ChemAxon
Number of Rings	2	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-03dl-7900000000-82f2ebd8b74ca296ae06	2021-09-23	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0532-0900000000-e31134aa571d68f62949	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00ei-0900000000-0aa0e3ad7c69dbd764af	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9300000000-14ded616dbe500acc3d0	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0002-0900000000-17ca17bff4342baf2ea4	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0a4j-1900000000-9bb2c6c50e2aaf1c5ddd	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-052f-9600000000-46d6f441fe573e243688	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0002-0900000000-5141251c4241c3b70bb3	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-000b-0900000000-f677d3548283e11f7354	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-008d-9400000000-35f0355727c4637e8ea2	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0a4j-6900000000-6538746085fac967dfb3	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0a4i-6900000000-9ddfe2dcf6691f0632eb	2021-10-12	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0a4l-9200000000-1e576b18d69f4123a41b	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-10-12	View Spectrum

Toxicity Profile

Route of Exposure

Oral, dermal, inhalation, and parenteral (contaminated drugs). (4)

Mechanism of Toxicity

Slaframine is a parasympathomimetic compound and causes increased secretion by salivary glands, pancreas, and other exocrine and endocrine glands. This is due to its activity as a cholingergic agonist. Slaframine has a high affinity for muscarinic receptors, especially in the gastrointestinal tract, and it stimulates these to produce its parasympathomimetic effects. Slaframine is also known to affect the concentration of circulating metabolic hormones, though the mechanism of this is unknown. (1, 2)

Metabolism

Slaframine is though to be activated in the liver by a hepatic microsomal flavoprotein oxidase to a ketoimine metabolite with a configuration similar to that of the parasympathetic neurotransmitter acetylcholine. (2)

Toxicity Values

Not Available

Lethal Dose

LD50: 11 mg/kg (Broiler chick) (3)

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Slaframine is a mycotoxin produced by the fungus Rizoctonia leguminicola. (1)

Minimum Risk Level

Not Available

Health Effects

Slaframine is a parasympathomimetic compound and causes increased exocrine function, especially salivation. Along with swainsonine, the other biologially active compound of R. leguminicola, it is known to cause a condition called "slobbers syndrome" in livestock that has ingested contaminated feed. (1, 2)

Symptoms

The major symptom of "slobbers syndrome" is profuse salivation. Other symptoms include diarrhea, lacrimation, stiff joints, frequent urination, tremors, spontaneous abortion, labored breathing, loss of appetite, bloat, and possibly death. (2)

Treatment

The effects of slaframine can be prevented by pre-treatment with an muscarinic receptor antagonist such as atropine or pirenzepine. (2)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

88363

ChEMBL ID

Not Available

ChemSpider ID

Not Available

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

Not Available

General References

Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]
Croom WJ Jr, Hagler WM Jr, Froetschel MA, Johnson AD: The involvement of slaframine and swainsonine in slobbers syndrome: a review. J Anim Sci. 1995 May;73(5):1499-508. [7665382 ]
Broquist HP: The indolizidine alkaloids, slaframine and swainsonine: contaminants in animal forages. Annu Rev Nutr. 1985;5:391-409. [3927948 ]
Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. 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

References

Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]
Croom WJ Jr, Hagler WM Jr, Froetschel MA, Johnson AD: The involvement of slaframine and swainsonine in slobbers syndrome: a review. J Anim Sci. 1995 May;73(5):1499-508. [7665382 ]

Target Details

2. 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

References

Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]
Croom WJ Jr, Hagler WM Jr, Froetschel MA, Johnson AD: The involvement of slaframine and swainsonine in slobbers syndrome: a review. J Anim Sci. 1995 May;73(5):1499-508. [7665382 ]

Target Details

3. 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

References

Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]
Croom WJ Jr, Hagler WM Jr, Froetschel MA, Johnson AD: The involvement of slaframine and swainsonine in slobbers syndrome: a review. J Anim Sci. 1995 May;73(5):1499-508. [7665382 ]

Target Details

4. 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

References

Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]
Croom WJ Jr, Hagler WM Jr, Froetschel MA, Johnson AD: The involvement of slaframine and swainsonine in slobbers syndrome: a review. J Anim Sci. 1995 May;73(5):1499-508. [7665382 ]

Target Details

5. 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

References

Chapa AM, Fernandez JM, Thompson DL Jr, Tempelman RJ, Berrio LF, Croom WJ Jr, Hagler WM Jr: Endocrine and metabolic response to muscarinic stimulation and inhibition in the ruminant: effects of slaframine. J Anim Sci. 1995 Dec;73(12):3673-80. [8655443 ]
Croom WJ Jr, Hagler WM Jr, Froetschel MA, Johnson AD: The involvement of slaframine and swainsonine in slobbers syndrome: a review. J Anim Sci. 1995 May;73(5):1499-508. [7665382 ]

Slaframine (T3D3775)

Structure for T3D3775: Slaframine

Targets

References

References

References

References

References