Identification

Name
Bioallethrin
Accession Number
DB13746
Type
Small Molecule
Groups
Approved, Experimental
Description

Bioallethrin refers to a mixture of two of the allethrin isomers (1R,trans;1R and 1R,trans;1S) in an approximate ratio of 1:1, where both isomers are active ingredients. A mixture of the two same stereoisomers, but in an approximate ratio of R:S in 1:3, is called esbiothrin. A mixture containing only S-forms of allethrin is referred to as esbioallethrin or S-bioallethrin. Bioallethrin is a synthetic pyrethroid used as a pesticide against household pest insects such as mosquitoes, houseflies and cockroaches. It is claimed to have low mammalian toxicity.

Synonyms
  • Depall├ęthrine
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Para Special Shampoo for Lice & NitsBioallethrin (1.1 %) + Piperonyl butoxide (4.4 %)ShampooTopicalMedican Technologies Inc.1989-12-312005-09-15Canada
ScabeneBioallethrin (0.63 %) + Piperonyl butoxide (5.04 %)AerosolTopicalMedican Technologies Inc.1997-06-102005-09-15Canada
Scabene AerosolBioallethrin (.63 %) + Piperonyl butoxide (5.04 %)AerosolTopicalStiefel Laboratories, Inc.1991-12-311997-11-19Canada
Categories
UNII
G79DM7O471
CAS number
584-79-2
Weight
Not Available
Chemical Formula
C19H26O3
InChI Key
ZCVAOQKBXKSDMS-AQYZNVCMSA-N
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

Bioallethrin was used for lice and scabies infestation. Other pyrethroids are now used in place of bioallethrin.

Pharmacodynamics

Bioallethrin causes respiratory paralysis in lice and scabies parasites resulting in death [1].

Mechanism of action

Bioallethrin, like other pyrethroids, binds to voltage gated sodium channels in their closed state and modifies the gating kinetics [1]. Channel opening appears to increase affinity of the channel for pyrethroids like bioallethrin. Once bound pyrethroids slow both the opening and closing of the sodium channel resulting in a need for stronger excitatory potentials to produce an action potential and a delay in repolarization. The these changes make the neuron more susceptible to large action potentials and repeated firing by both increasing the initial threshold and reducing the input needed for after-potentials. When repeated firing does occur, the nerve terminal will release more neurotransmitter which can produce muscle paralysis through tetanus. This paralysis stops the breathing of lice and scabies parasites resulting in death.

Some pyrethroids act on calcium channels to increase intracelllular calcium [2]. Bioallethrin produces a very small increase in intracellular calcium in mouse neocortical neurons by acting on N-type calcium channels but the effect returns to baseline within 2 min. In contrast bioallethrin has been found to block L T, and P/Q-types of voltage gated calcium channels in human embryonic kidney cell cultures [6]. Bioallethrin has been found to inhibit both sodium-calcium dependent and magnesium-calcium ATP hydrolysis in insects although it, along with other type I pyrethroids, has a greater effect on sodium-calcium dependent hydrolysis [3]. Bioallethrin may stimulate phosphoinositol breakdown in synaptoneuromes as other type I pyrethroids have been observed to do so [4]. Other type I pyrethoids have also been found to bind to kainate receptors [5].

TargetActionsOrganism
UVoltage gated sodium channel
modulator
human
ASodium channel protein
modulator
Pediculus humanus
UVoltage-dependent N-type calcium channel
agonist
Human
UVoltage-dependent T-type calcium channel
blocker
Homo sapiens
UVoltage-dependent P/Q-type calcium channel
blocker
Homo sapiens
UVoltage dependent L type calcium channel
blocker
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolism of bioallethrin in both rats and humans is considered to be virtually 100% oxidative [7, 8]. This is because bioallethrin is very resistant to hydrolysis of its ester group although a negligible amount of hydrolysis may occur.

In humans bioallethrin is metabolized primarily by CYP2C19 with some metabolism by CYP2C8, CYP3A4, and CYP2C9*2 [7]. The metabolites produced include primary alcohols via allylic oxidation near the cyclopropane group and subsequent oxidation to carboxylic acid, formation of a primary alcohol via oxidation of a methyl group to located on the cyclopropane portion of the molecule, formation of a primary alcohol via allylic oxidation near the 5-membered ring or formation of an epoxide at this location and subsequent hydrolysis to a diol.

In rats bioallethrin has been found to be metabolized mainly by CYP2C6, CYP2C11, and CYP3A1 with some contribution from CYP1A1, CYP2A1 and CYP3A2 [7]. Rats appear to metabolize bioallethrin at about 15 times the rate of humans.

Route of elimination

Pyrethroids are excreted in both the feces and urine but values specific to bioallethrin are not available [8].

Half life
Not Available
Clearance
Not Available
Toxicity

Bioallethrin can produce hypersensitivity reactions in patients sensitive to ragweed or chrysanthemum [10]. Ingestion of bioallethrin can produce life-threatening convulsions or coma. Less serious toxic effects include sore throat, nausea, vomiting, abdominal pain, mouth ulceration, increased secretions and/or dysphagia. Systemic effects include dizziness, headache and fatigue are common, and palpitations, chest tightness and blurred vision and occur 4-48 h after exposure.

Bioallethrin is not carcinogenic or mutagenic [9]. In rats doses over 58.7 mg/kg/day produce reproductive effects and doses over 125 mg/kg/day are embryotoxic.

Observed LD50 for various routes in animal studies [9]:

Rat

  • Male Oral - 709 mg/kg
  • Female Oral - 1040 mg/kg
  • Inhalation - 2.51 mg/L

Rabbit

  • Dermal - >3000 mg/kg
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbafunginThe therapeutic efficacy of Abafungin can be increased when used in combination with Bioallethrin.
AcepromazineThe risk or severity of hypotension can be increased when Acepromazine is combined with Bioallethrin.
AlbaconazoleThe therapeutic efficacy of Albaconazole can be increased when used in combination with Bioallethrin.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Bioallethrin.
AlcuroniumBioallethrin may increase the neuromuscular blocking activities of Alcuronium.
AlfuzosinThe risk or severity of hypotension can be increased when Alfuzosin is combined with Bioallethrin.
AmcinonideThe metabolism of Amcinonide can be decreased when combined with Bioallethrin.
Aminosalicylic AcidBioallethrin may increase the anticoagulant activities of Aminosalicylic Acid.
AmiodaroneThe metabolism of Bioallethrin can be decreased when combined with Amiodarone.
AmitriptylineThe metabolism of Amitriptyline can be decreased when combined with Bioallethrin.
Food Interactions
Not Available

References

General References
  1. Narahashi T: Neuronal ion channels as the target sites of insecticides. Pharmacol Toxicol. 1996 Jul;79(1):1-14. [PubMed:8841090]
  2. Cao Z, Shafer TJ, Murray TF: Mechanisms of pyrethroid insecticide-induced stimulation of calcium influx in neocortical neurons. J Pharmacol Exp Ther. 2011 Jan;336(1):197-205. doi: 10.1124/jpet.110.171850. Epub 2010 Sep 29. [PubMed:20881019]
  3. Clark JM, Matsumura F: The action of two classes of pyrethroids on the inhibition of brain Na-Ca and Ca + Mg ATP hydrolyzing activities of the American cockroach. Comp Biochem Physiol C. 1987;86(1):135-45. [PubMed:2881709]
  4. Gusovsky F, Hollingsworth EB, Daly JW: Regulation of phosphatidylinositol turnover in brain synaptoneurosomes: stimulatory effects of agents that enhance influx of sodium ions. Proc Natl Acad Sci U S A. 1986 May;83(9):3003-7. [PubMed:2422664]
  5. Staatz CG, Bloom AS, Lech JJ: Effect of pyrethroids on [3H]kainic acid binding to mouse forebrain membranes. Toxicol Appl Pharmacol. 1982 Jul;64(3):566-9. [PubMed:7135402]
  6. Hildebrand ME, McRory JE, Snutch TP, Stea A: Mammalian voltage-gated calcium channels are potently blocked by the pyrethroid insecticide allethrin. J Pharmacol Exp Ther. 2004 Mar;308(3):805-13. doi: 10.1124/jpet.103.058792. Epub 2003 Nov 21. [PubMed:14634047]
  7. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]
  8. Miyamoto J: Degradation, metabolism and toxicity of synthetic pyrethroids. Environ Health Perspect. 1976 Apr;14:15-28. [PubMed:789062]
  9. WHO SPECIFICATIONS AND EVALUATIONS FOR PUBLIC HEALTH PESTICIDES: Bioallethrin [Link]
  10. HSDB: Allethrins [Link]
External Links
PubChem Compound
15558638
PubChem Substance
347829312
ChemSpider
18923353
ChEBI
39118
ChEMBL
CHEMBL1788403
Wikipedia
Bioallethrin
ATC Codes
P03AC02 — BioallethrinP03AC52 — Bioallethrin, combinations
MSDS
Download (273 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
ShampooTopical
AerosolTopical
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
boiling point (┬░C)165-170WHO SPECIFICATIONS AND EVALUATIONS FOR PUBLIC HEALTH PESTICIDES : BIOALLETHRIN
water solubility4.6 mg/LWHO SPECIFICATIONS AND EVALUATIONS FOR PUBLIC HEALTH PESTICIDES : BIOALLETHRIN
logP4.7WHO SPECIFICATIONS AND EVALUATIONS FOR PUBLIC HEALTH PESTICIDES : BIOALLETHRIN
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

1. Voltage gated sodium channel
Kind
Protein group
Organism
human
Pharmacological action
Unknown
Actions
Modulator
Curator comments
Bioallethrin slows the opening and closing of the channel.
References
  1. Narahashi T: Neuronal ion channels as the target sites of insecticides. Pharmacol Toxicol. 1996 Jul;79(1):1-14. [PubMed:8841090]
Kind
Protein
Organism
Pediculus humanus
Pharmacological action
Yes
Actions
Modulator
Curator comments
Bioallethrin slows the opening and closing of the channel.
General Function
Mediates the voltage-dependent sodium ion permeability of excitable membranes.
Specific Function
Calcium ion binding
Gene Name
Not Available
Uniprot ID
Q86DI9
Uniprot Name
Sodium channel protein
Molecular Weight
233296.52 Da
References
  1. Narahashi T: Neuronal ion channels as the target sites of insecticides. Pharmacol Toxicol. 1996 Jul;79(1):1-14. [PubMed:8841090]
3. Voltage-dependent N-type calcium channel
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
Curator comments
Seems to be a weak agonist at N-type but blocker at L, T, and P/Q-type.
References
  1. Cao Z, Shafer TJ, Murray TF: Mechanisms of pyrethroid insecticide-induced stimulation of calcium influx in neocortical neurons. J Pharmacol Exp Ther. 2011 Jan;336(1):197-205. doi: 10.1124/jpet.110.171850. Epub 2010 Sep 29. [PubMed:20881019]
Kind
Protein group
Organism
Homo sapiens
Pharmacological action
Unknown
Actions
Blocker
General Function
Scaffold protein binding
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...

Components:
References
  1. Hildebrand ME, McRory JE, Snutch TP, Stea A: Mammalian voltage-gated calcium channels are potently blocked by the pyrethroid insecticide allethrin. J Pharmacol Exp Ther. 2004 Mar;308(3):805-13. doi: 10.1124/jpet.103.058792. Epub 2003 Nov 21. [PubMed:14634047]
Kind
Protein group
Organism
Homo sapiens
Pharmacological action
Unknown
Actions
Blocker
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...

Components:
References
  1. Hildebrand ME, McRory JE, Snutch TP, Stea A: Mammalian voltage-gated calcium channels are potently blocked by the pyrethroid insecticide allethrin. J Pharmacol Exp Ther. 2004 Mar;308(3):805-13. doi: 10.1124/jpet.103.058792. Epub 2003 Nov 21. [PubMed:14634047]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Blocker
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...

Components:
References
  1. Hildebrand ME, McRory JE, Snutch TP, Stea A: Mammalian voltage-gated calcium channels are potently blocked by the pyrethroid insecticide allethrin. J Pharmacol Exp Ther. 2004 Mar;308(3):805-13. doi: 10.1124/jpet.103.058792. Epub 2003 Nov 21. [PubMed:14634047]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Curator comments
Only metabolized by the CYP2C9*2 variant.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]
Kind
Protein
Organism
Rat
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Highly active in the 7-alpha-hydroxylation of testosterone, progesterone and androstenedione.
Gene Name
Cyp2a1
Uniprot ID
P11711
Uniprot Name
Cytochrome P450 2A1
Molecular Weight
55994.635 Da
References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]
Kind
Protein
Organism
Rat
Pharmacological action
No
Actions
Substrate
General Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Specific Function
Aromatase activity
Gene Name
Cyp1a1
Uniprot ID
P00185
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
59392.695 Da
References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]
Kind
Protein
Organism
Rat
Pharmacological action
No
Actions
Substrate
General Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Specific Function
Arachidonic acid epoxygenase activity
Gene Name
Cyp2c6
Uniprot ID
P05178
Uniprot Name
Cytochrome P450 2C6
Molecular Weight
56002.315 Da
References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]
Kind
Protein
Organism
Rat
Pharmacological action
No
Actions
Substrate
General Function
Metabolizes testosterone mainly in positions 2 alpha and 16 alpha.
Specific Function
Arachidonic acid epoxygenase activity
Gene Name
Cyp2c11
Uniprot ID
P08683
Uniprot Name
Cytochrome P450 2C11
Molecular Weight
57180.595 Da
References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]
Kind
Protein
Organism
Rat
Pharmacological action
No
Actions
Substrate
General Function
Testosterone 6-beta-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
Cyp3a1
Uniprot ID
P04800
Uniprot Name
Cytochrome P450 3A1
Molecular Weight
57917.375 Da
References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]
Kind
Protein
Organism
Rat
Pharmacological action
No
Actions
Substrate
General Function
Testosterone 6-beta-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
Cyp3a2
Uniprot ID
P05183
Uniprot Name
Cytochrome P450 3A2
Molecular Weight
57731.215 Da
References
  1. Scollon EJ, Starr JM, Godin SJ, DeVito MJ, Hughes MF: In vitro metabolism of pyrethroid pesticides by rat and human hepatic microsomes and cytochrome p450 isoforms. Drug Metab Dispos. 2009 Jan;37(1):221-8. doi: 10.1124/dmd.108.022343. Epub 2008 Oct 23. [PubMed:18948380]

Drug created on June 23, 2017 14:47 / Updated on August 26, 2018 02:06