Identification

Name
Icaridin
Accession Number
DB14074
Type
Small Molecule
Groups
Experimental
Description

Icaridin, also known as Picaridin or hydroxy-ethyl isobutyl piperidine carboxylate, is a cyclic amine and a member of the piperidine chemical family. Piperidines are structural components of Piperine, which is a plant extract from the genus _Piper _, or pepper. Icaridin has been commonly used as a topically-applied insect repellent in various countries but was officially licensed for use in the United States in 2001 and Canada in 2012 [4]. Icaridin was synthesized by Bayer in the 1980s based on molecular modeling [4]. It is considered to be the first choice of repellent by the Public Health Agency of Canada’s Canadian Advisory Committee on Tropical Medicine and Travel for travelers six months to 12 years of age [1]. Icaridin is reported to be less irritating than Diethyltoluamide, another common insect repellant, and products containing up to 20% of icaridin are considered safe for long-term use in adults [3].

Structure
Thumb
Synonyms
  • Icaridin
  • Icaridina
  • Icaridinum
  • Picaridin
  • Pikaridin
  • Propidine
External IDs
EC 423-210-8 / KBR 3023
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SG Plus Repellent Aroma MistLiquid2.1 g/30mLTopicalHankook Samgong Co.,ltd2017-06-27Not applicableUs
International/Other Brands
Bayrepel / Saltidin
Categories
UNII
N51GQX0837
CAS number
119515-38-7
Weight
Average: 229.3159
Monoisotopic: 229.167793607
Chemical Formula
C12H23NO3
InChI Key
QLHULAHOXSSASE-UHFFFAOYSA-N
InChI
InChI=1S/C12H23NO3/c1-3-10(2)16-12(15)13-8-5-4-6-11(13)7-9-14/h10-11,14H,3-9H2,1-2H3
IUPAC Name
butan-2-yl 2-(2-hydroxyethyl)piperidine-1-carboxylate
SMILES
CCC(C)OC(=O)N1CCCCC1CCO

Pharmacology

Indication

Icaridin is indicated for use to repel insects via topical use or over clothing [5].

Pharmacodynamics

Icaridin is a cyclic amine and piperidine compound that is expected to stimulate the sensory hairs on the antennae of insects [4].

Mechanism of action

The exact mechanism and target molecules of icaridin repelling insects are not fully understood; it is presumed that piperine interacts with the olfactory system consisting of odorant receptors (ORs) that need a common co-receptor (ORCO), and of ionotropic receptors (IR) [3], leading to the insect's inability to recognize its host's cues [4]. It is also suggested that icaridin may bind to odorant binding protein 1 (AgamOBP1) at different binding sites [2]. A study demonstrated that icaridin inhibited the odorant-induced responses of AaOR2 and AaOR8 expressed in Xenopus oocytes, leading to altered olfactory inputs by olfactory sensory neurons (OSN) [3].

TargetActionsOrganism
AOdorant binding protein
ligand
Anopheles gambiae
Absorption

In a dermal metabolism rat study, dermal application of 20 mg/kg of radio-labeled icaridin resulted in 61-66% of the dose absorbed through the skin [4]. Following topical application of 20 mg/kg on rats, the peak plasma concentrations were measured to be 0.5 μg/mL in male rats and 0.8-1.6 μg/mL in female rats [4].

Volume of distribution

There is no available information on the volume of distribution of icaridin.

Protein binding

There is no available information on the protein binding of icaridin.

Metabolism

While icaridin may undergo Phase I metabolic reactions, there is limited data on the metabolism of the drug [4].

Route of elimination

Following topical administration on rats at doses of 20 mg/kg, urinary excretion was reported to be the primary route of elimination where 73-88% of the parent compound was recovered in the urine [4]. At doses of 200 mg/kg, the 40% of the administered dose was excreted in the urine or feces [4].

Half life

There is no available information on the half life of icaridin.

Clearance

There is no available information on the clearance of icaridin.

Toxicity

Oral LD50 values in fasted and non-fasted male rats were 2236 mg/kg and 4743 mg/kg, respectively [4]. Acute dermal LD50 values in rats were greater than 2000 mg/kg and 5000 mg/kg [4].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Onyett H: Preventing mosquito and tick bites: A Canadian update. Paediatr Child Health. 2014 Jun;19(6):326-32. [PubMed:25332663]
  2. Drakou CE, Tsitsanou KE, Potamitis C, Fessas D, Zervou M, Zographos SE: The crystal structure of the AgamOBP1*Icaridin complex reveals alternative binding modes and stereo-selective repellent recognition. Cell Mol Life Sci. 2017 Jan;74(2):319-338. doi: 10.1007/s00018-016-2335-6. Epub 2016 Aug 17. [PubMed:27535661]
  3. Van Roey K, Sokny M, Denis L, Van den Broeck N, Heng S, Siv S, Sluydts V, Sochantha T, Coosemans M, Durnez L: Field evaluation of picaridin repellents reveals differences in repellent sensitivity between Southeast Asian vectors of malaria and arboviruses. PLoS Negl Trop Dis. 2014 Dec 18;8(12):e3326. doi: 10.1371/journal.pntd.0003326. eCollection 2014 Dec. [PubMed:25522134]
  4. Gervais, J. A.; Wegner, P.; Luukinen, B.; Buhl, K.; Stone, D. 2009. Picaridin Technical Fact Sheet; National Pesticide Information Center, Oregon State University Extension Services. [Link]
  5. DailyMed - SG PLUS REPELLENT AROMA MIST- icaridin liquid [Link]
  6. Health Canada Icaridin Evaluation [File]
External Links
ChemSpider
111359
ChEMBL
CHEMBL2104314
Wikipedia
Icaridin
MSDS
Download (22.5 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
LiquidTopical2.1 g/30mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolublePicaridin Technical Fact Sheet; National Pesticide Information Center, Oregon State University Extension Services
Predicted Properties
PropertyValueSource
Water Solubility25.1 mg/mLALOGPS
logP2.19ALOGPS
logP1.61ChemAxon
logS-0.96ALOGPS
pKa (Strongest Acidic)15.92ChemAxon
pKa (Strongest Basic)-2.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area49.77 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity62.54 m3·mol-1ChemAxon
Polarizability26.24 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Anopheles gambiae
Pharmacological action
Yes
Actions
Ligand
General Function
Not Available
Specific Function
Odorant binding
Gene Name
OBP-1
Uniprot ID
Q8T6S0
Uniprot Name
Odorant binding protein
Molecular Weight
16538.985 Da
References
  1. Drakou CE, Tsitsanou KE, Potamitis C, Fessas D, Zervou M, Zographos SE: The crystal structure of the AgamOBP1*Icaridin complex reveals alternative binding modes and stereo-selective repellent recognition. Cell Mol Life Sci. 2017 Jan;74(2):319-338. doi: 10.1007/s00018-016-2335-6. Epub 2016 Aug 17. [PubMed:27535661]

Drug created on June 16, 2018 17:17 / Updated on December 14, 2018 16:31