Record Information
Version2.0
Creation Date2010-05-27 08:58:19 -0600
Update Date2014-11-04 15:52:59 -0700
Accession NumberT3D3775
Identification
Common NameSlaframine
ClassSmall Molecule
DescriptionSlaframine 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
Thumb
Synonyms
Synonym
(1S,6S,8aS)-1-Acetoxy-6-aminooctahydroindolizine
(1S-(1alpha,6alpha,8abeta))-6-Aminooctahydro-1-indolizinol, acetate (ester)
Chemical FormulaC10H18N2O2
Average Molecular Mass198.262 g/mol
Monoisotopic Mass198.137 g/mol
CAS Registry Number20084-93-9
IUPAC Name6-amino-octahydroindolizin-1-yl acetate
Traditional Nameslaframine
SMILESCC(=O)OC1CCN2CC(N)CCC12
InChI IdentifierInChI=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 KeyInChIKey=YYIUHLPAZILPSG-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassHeterocyclic Compounds
ClassIndolizidines
Sub ClassNot Available
Direct ParentIndolizidines
Alternative Parents
Substituents
  • Primary Amine
  • Organonitrogen Compound
  • Carboxylic Acid Ester
  • Piperidine
  • Tertiary Amine
  • Pyrrolidine
  • Indolizidine
  • 3-aminopiperidine
  • Ether
  • Organooxygen Compound
  • Carbonyl Group
  • Carboxylic Acid Derivative
  • N-alkylpyrrolidine
  • Amine
  • Aliphatic Heteropolycyclic Compound
  • Primary Aliphatic Amine
  • Acetate Salt
  • Monocarboxylic Acid Or Derivatives
Molecular FrameworkAliphatic Heteropolycyclic Compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility250.0ALOGPS
logP-0.07ALOGPS
logP-0.38ChemAxon
logS0.1ALOGPS
pKa (Strongest Basic)9.82ChemAxon
Physiological Charge2ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area55.56 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity52.83 m3·mol-1ChemAxon
Polarizability21.7 Å3ChemAxon
Spectra
SpectraNot Available
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (4)
Mechanism of ToxicitySlaframine 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)
MetabolismSlaframine 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 ValuesNot Available
Lethal DoseLD50: 11 mg/kg (Broiler chick) (3)
Carcinogenicity (IARC Classification)Not Available
Uses/SourcesSlaframine is a mycotoxin produced by the fungus Rizoctonia leguminicola. (1)
Minimum Risk LevelNot Available
Health EffectsSlaframine 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)
SymptomsThe 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)
TreatmentThe 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
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID88363
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. 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 ]
  2. 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 ]
  3. Broquist HP: The indolizidine alkaloids, slaframine and swainsonine: contaminants in animal forages. Annu Rev Nutr. 1985;5:391-409. [3927948 ]
  4. 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 GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Involved in rhodopsin-like 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:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51421.0 Da
References
  1. 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 ]
  2. 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 ]
General Function:
Involved in rhodopsin-like 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
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51716.0 Da
References
  1. 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 ]
  2. 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 ]
General Function:
Involved in rhodopsin-like 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:
66129.0 Da
References
  1. 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 ]
  2. 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 ]
General Function:
Involved in rhodopsin-like 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 inhibition of adenylate cyclase
Gene Name:
CHRM4
Uniprot ID:
P08173
Molecular Weight:
53050.0 Da
References
  1. 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 ]
  2. 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 ]
General Function:
Involved in rhodopsin-like 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:
CHRM5
Uniprot ID:
P08912
Molecular Weight:
60074.0 Da
References
  1. 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 ]
  2. 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 ]