Record Information
Version 1.0
Creation Date 2010-05-27 08:58:19 -0600
Update Date 2014-08-11 10:36:19 -0600
Accession Number T3D3775
Identification
Common Name Slaframine
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. (A3091, A3092)
Compound Type
  • Organic Compound
  • Mycotoxin
Chemical Structure
Thumb
Synonyms
  1. (1S,6S,8aS)-1-Acetoxy-6-aminooctahydroindolizine
  2. (1S-(1alpha,6alpha,8abeta))-6-Aminooctahydro-1-indolizinol, acetate (ester)
Chemical Formula C10H18N2O2
Average Molecular Weight 198.2621
Monoisotopic Molecular Weight 198.13682783
IUPAC Name
6-amino-octahydroindolizin-1-yl acetate
Traditional IUPAC Name
6-amino-octahydroindolizin-1-yl acetate
CAS Registry Number 20084-93-9
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
Kingdom Organic Compounds
Super Class Heterocyclic Compounds
Class Indolizidines
Sub Class Not Available
Direct Parent Indolizidines
Alternative Parents
  • Aminopiperidines
  • Pyrrolidines
  • Trialkylamines
  • Carboxylic Acid Esters
  • Enolates
  • Alkylamines
Molecular Framework Aliphatic Heteropolycyclic Compounds
Substituents
  • primary amine
  • organonitrogen compound
  • carboxylic acid ester
  • enolate
  • piperidine
  • tertiary aliphatic amine (trialkylamine)
  • tertiary amine
  • pyrrolidine
  • primary aliphatic amine (alkylamine)
  • 3-aminopiperidine
External Descriptors Not Available
Biological Properties
Status Unknown/Not Detected
Origin Not Available
Cellular Locations Not Available
Biofluid Locations Not Available
Tissue Locations Not Available
Pathways Not Available
Physical Properties
State Not Available
Appearance Not Available
Experimental Properties
Property Value
Melting Point Not Available
Boiling Point Not Available
Solubility Not Available
LogP Not Available
Predicted Properties
PropertyValueSource
water solubility2.50e+02 g/lALOGPS
logP-0.07ALOGPS
logP-0.38ChemAxon
logS0.1ALOGPS
pKa (strongest basic)9.82ChemAxon
physiological charge2ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count1ChemAxon
polar surface area55.56ChemAxon
rotatable bond count2ChemAxon
refractivity52.83ChemAxon
polarizability21.7ChemAxon
Spectra
Spectra Not Available
Toxicity Profile
Route of Exposure Oral, dermal, inhalation, and parenteral (contaminated drugs). (A3101)
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. (A3091, A3092)
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. (A3092)
Toxicity Values Not Available
Lethal Dose LD50: 11 mg/kg (Broiler chick) (A3093)
Carcinogenicity (IARC Classification) Not Available
Uses/Sources Slaframine is a mycotoxin produced by the fungus Rizoctonia leguminicola. (A3091)
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. (A3091, A3092)
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. (A3092)
Treatment The effects of slaframine can be prevented by pre-treatment with an muscarinic receptor antagonist such as atropine or pirenzepine. (A3092)
Normal Concentrations
Not Available
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 Not Available
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
General References
  • A3091 — 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 ]
  • A3092 — 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 ]
  • A3093 — Broquist HP: The indolizidine alkaloids, slaframine and swainsonine: contaminants in animal forages. Annu Rev Nutr. 1985;5:391-409. [3927948 ]
  • A3101 — Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]

Targets

1. Muscarinic acetylcholine receptor M3

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.

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. (A3091, A3092)
UniProt ID: P20309
Gene: CHRM3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A3091 — 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 ]
  • A3092 — 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 ]

2. Muscarinic acetylcholine receptor M1

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.

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. (A3091, A3092)
UniProt ID: P11229
Gene: CHRM1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A3091 — 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 ]
  • A3092 — 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. Muscarinic acetylcholine receptor M2

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.

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. (A3091, A3092)
UniProt ID: P08172
Gene: CHRM2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A3091 — 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 ]
  • A3092 — 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 ]

4. Muscarinic acetylcholine receptor M4

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.

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. (A3091, A3092)
UniProt ID: P08173
Gene: CHRM4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A3091 — 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 ]
  • A3092 — 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 ]

5. Muscarinic acetylcholine receptor M5

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.

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. (A3091, A3092)
UniProt ID: P08912
Gene: CHRM5
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
  • A3091 — 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 ]
  • A3092 — 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 ]