XPharm Agent Leaf (Base) Record, v1
Elsevier Science, Inc., 2001
Record for an Individual AGENT
Record Data
Record Name:
6-Iodonordihydrocapsaicin
Record Author(s):
Roche, Michelle; Finn, David
Description
Introduction:6-Iodonordihydrocapsaicin was first synthesized by Giovanni Appendino at the Department of Chemical, Food,
Pharmaceutical and Pharmacological Sciences (DiSCAFF), Novara, Italy, while developing a series of halogenated
derivatives of capsaicin (Appendino et al., 2003). This compound is a potent antagonist at the vanilloid VR-1 (TRPV1)
receptor in several in vitro preparations. Its activity in vivo has not been examined. Recent evidence indicates that 6iodonordihydrocapsaicin may also antagonize transient receptor potential channels of melastatin type 8 (TRPM8) (De
Petrocellis et al., 2007)
Nomenclature
Name of the Clinical Form:
6-Iodononivamide; N-(4-Hydroxy-6-iodo-3-methoxybenzyl)nonanamide
Synonyms and6-Iodonordihydrocapsaicin;
Trade Names:
Chemical Names:
859171-97-4
CAS Registry Number:
Basic Chemistry
Chemical Structure
Structure:
Comments:
C17H26INO3
Chemical Formula:
Properties
Physical Properties:
White powder
Molecular Weight:
419.3
Solubility:
Soluble to 50 mM in Ethanol and to 100 mM in DMSO
Ionization Constant
Value
Salt
Conditions
Reference
Comments
pka
Peptide Agents
Value
Comments
GenBank Accession #
# of Amino Acid Residues
Inhaled Anesthetics
Value
Minimum Alveolar
Concentration
Blood-Gas Partition
CoEf.
Units
Reference
Comments
Human Pharmacokinetics
Overview:
Pharmacokinetic Properties
Value
Units
Prep. and Route
of Admin.
Reference
Comments
Absorption
Bioavailability
Distribution
Volume of Distribution
Plasma Protein Binding
Metabolism
Plasma Half-Life
Biological Half-Life
Clearance
Routes of Elimination
Targets-Pharmacodynamics
Overview:
6-Iodonordihydrocapsaicin is a potent competitive vanilloid TRPV1 receptor antagonist and also acts as an
antagonist at TRPM8. Evidence from in vitro studies suggests that 6-iodonordihydrocapsaicin likely shares the
same binding site as capsaicin on the human TRPV1 with a 2-10 fold greater affinity than capsazepine for this site
(Appendino et al., 2003). 5-iodoresiniferatoxin (5-iodo-RTX) is more potent at the human TRPV1 receptor than 6Iiodonordihydrocapsaicin, which in turn is more potent than capsazepine and SB-366791 (Appendino et al., 2003).
Target Name(s):
TRPV1 (VR-1) Vanilloid receptor and transient receptor potential channels of melastatin type 8 (TRPM8).
Therapeutics
Overview:
Indications
Indication
Description:
Value
Units
Prep. and Route
of Admin.
Reference
Comments
Dosage
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Contraindications:
Adverse Effects:
Agent-Agent Interactions
Name
Mode of Interaction
Interaction Agent
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Preclinical Research
Overview:
To date, the activity of 6-iodonordihydrocapsaicin has only been examined in in vitro preparations. C-6 iodination of
nordihydrocapsaicin results in the development of a potent competitive antagonist of TRPV1 receptors. 6Iodonordihydrocapsaicin is more potent than capsazepine at blocking capsaicin-induced increases in [Ca2+]i at both
human and rat TRPV1 receptors (Appendino et al., 2003). Recent studies indicate that 6-iodonordihydrocapsaicin also
antagonizes TRPM8 receptors (De Petrocellis et al., 2007).
Pharmacokinetics
Overview:
Pharmacokinetic Properties
Organism Name:
Value
Units
Prep. and Route
of Admin.
Reference
Comments
Absorption
Bioavailability
Distribution
Volume of Distribution
Plasma Protein Binding
Metabolism
Plasma Half-Life
Biological Half-Life
Clearance
Routes of Elimination
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Potency
Organism Human Embryonic Kidney (HEK)-293 cells
Name:
Value
Units Organ/ Prep. and Route Cell Line/Type
Tissue
of Admin.
Dose
Effects
Exp. End Reference
Point
Comments
LD50
ED50
IC50
10.0  2.1 nM
Conc
10
nM
Conc
25
nM
Conc
10
nM
Conc
10
M
Conc
50
M
Conc
10
M
Organism Rat
Name:
HEK-293 cells Inhibition of capsaicin
overexpressing (100 nM)-induced
human TRPV1 increase in [Ca2+]i
HEK-293
Inhibition of capsaicin
overexpressing (100 nM)- induced
human
increase in [Ca2+]i.
TRPV1.
Appendino
et al., 2003;
2005
Appendino Schild plot slope
et al., 2003 = 0.86. Kd = 4.3
nM. More potent
than
capsazepine
(100 nM)
HEK-293
Inhibition of
overexpressing thapsigargin (1 M)human
induced increase in
TRPV1.
[Ca2+]i
HEK-293
Inhibition of cobalt
overexpressing uptake induced by
human
OAG (1-oleoyl-2TRPV1.
acetyl-sn-glycerol)
(100 M) and
capsaicin (1 M).
HEK-293
Inhibition of methanol
overexpressing (100 mM ) and icilin
human
(0.5 M) induced
TRPM8.
increase in [Ca2+]i.
(42.5 and 44.8%
inhibition respectively)
Van der Stelt
et al., 2005
Woo et al.,
2008
De
Petrocellis et
al., 2007
Value
Units
Organ/
Tissue
Prep. and Route Cell Line/Type
of Admin.
Effects
Exp. End
Point
Reference
Comments
Dose
LD50
ED50
IC50
638.6
nM
Conc
0.0001– M
100
Conc
10
 mol/l
Organism Guinea-Pig
Name:
Value
Units
Dose
1, 10
M
Dose
1, 10
M
Dose
1, 10
M
Neonatal rat
dorsal root
ganglia
neurons
Neonatal
dorsal root
ganglia
neurons
Rat uterine
strips.
Organ/
Tissue
Prep. and Route
Cell
of Admin.
Line/Type
Inhibition of capsaicin
(100 nM)- induced
[Ca2+]i
Appendino
et al., 2003
Inhibition of capsaicin
(100 nM)- induced
[Ca2+]i.
Appendino
et al., 2003
No effect on
veratridine (voltage
gated Na+ channel
activator) (60 M)induced contraction.
Seda et al.,
2007
Effects
4 times more
potent than
capsazepine.
Exp. End Reference
Comments
Point
Appendino More potent than
et al.,
capsazepine (pA2 =
2003
7.17 vs 6.56 for
capsazepine)
Guinea-pig urinary
bladder.
Dose dependant
inhibition of
capsaicin (0.1 nM–
100 M)-mediated
contractions
Appendino Guinea-pig urinary
et al.,
bladder
2003
No effect on
substance P (0.1
nM–100 M)mediated
contractions
Appendino Less potent than
et al.,
capsazepine (pA2 =
2003
5.6 vs 7.0 for
capsazepine)
Guinea-pig trachea.
Inhibition of
capsaicin (0.1 nM–
100 M) -induced
contractions
LD50
ED50
IC50
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Repeat for each new organism.
When a constant varies with different assay conditions, insert a new row, and copy the appropriate constant label into the gray cell at the left.
Other Research Information:
Other Information
Websites: A PubChem compound summary is available at: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=24895913
Further Reading:
Breaking News
Bibliographic References
Journal Citations
Author(s)
Article Title
Appendino, G., Harrison, S., De
Petrocellis, L., Daddario, N., Bianchi, F.,
Moriello, A.S., Trevisani, M., Benvenuti,
F., Geppetti, P. and Di Marzo, V.
Appendino, G., Daddario, N., Minassi,
A., Moriello, A.S., De Petrocellis, L. and
Di Marzo, V.
De Petrocellis, L., Starowicz, K.,
Moriello, A.S., Vivese, M., Orlando, P.
and Di Marzo, V.
Journal
Halogenation of a capsaicin analogue leads to Br. J. Pharmacol.
novel vanilloid TRPV1 receptor antagonists
The taming of capsaicin. Reversal of the
vanilloid activity of N-acylvanillamines by
aromatic iodination
Regulation of transient receptor potential
channels of melastatin type 8 (TRPM8): effect
of cAMP, cannabinoid CB1 receptors and
endovanilloids
Sada, M., Pinto, F.M., Wray, S.,
Functional and molecular characterization of
Cintado, C., Noheda, P., Buschmann, H. voltage-gated sodium channels in uteri from
and Candenas, L.
non-pregnant rats
Van der Stelt, M., Trevisani, M., Vellani, Anandamide acts as an intracellular
V., De Petrocellis, L., Moriello, A.S.,
messenger amplifying Ca2+ influx via TRPV1
Campi, B., McNaughton, P., Geppetti, P. channels
and Di Marzo, V.
Woo, D.H., Jung, S.J., Zhu, M.H., Park, Direct activation of transient receptor potential
C., Kim, Y.H., Oh, S.B. and Lee, C.J.
vanilloid 1 (TRPV1) by diacylglycerol (DAG)
Year Vol(Issue) Page(s)
2003 139
14171424
J. Med. Chem.
2005 48(14)
46634669
Exp. Cell. Res.
2007 313
19111920
Biol. Reprod.
2007 77
855863
EMBO Rep.
2005 24
30263037
Mol. Pain.
2008 4:42
1-15
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Repeat for each new journal citation.
Book Citations
Author(s)
Editor(s)
Title of Chapter
Title of Book
Page(s)
Edition
Year
Publisher
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End of Record for an Individual AGENT
Reviewer's Comments
A good record.
Vera (6-5-2009)
Place