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Identification
NameLindane
Accession NumberDB00431  (APRD01072)
Typesmall molecule
Groupsapproved, withdrawn
Description

An organochlorine insecticide that has been used as a pediculicide and a scabicide. Lindane has been banned in California, United Kingdom, Australia, and many western countries due to concerns about neurotoxicity and adverse effects on the environment. In Canada, Lindane is not recommmended as a first-line therapy due to reports of resistance, neurotoxicity, and bone marrow suppression, but has been approved by the FDA as a second-line therapy for topical treatment of pediculosis capitis (head lice), pediculosis pubis (pubic lice), or scabies in patients greater than two years of age who cannot tolerate or have failed first-line treatment.

Structure
Thumb
Synonyms
SynonymLanguageCode
(1alpha,2alpha,3beta,4alpha,5alpha,6beta)-1,2,3,4,5,6-HexachlorocyclohexaneNot AvailableNot Available
(1R,2c,3t,4c,5c,6t)-1,2,3,4,5,6-HexachlorocyclohexaneNot AvailableNot Available
1,2,3,4,5,6-HexachlorocyclohexaneNot AvailableNot Available
Benzene hexachlorideNot AvailableNot Available
gamma-1,2,3,4,5,6-HexachlorocyclohexaneNot AvailableNot Available
gamma-Benzene hexachlorideNot AvailableNot Available
gamma-BHCNot AvailableNot Available
gamma-HCHNot AvailableNot Available
gamma-HexachlorocyclohexaneNot AvailableNot Available
gamma-HexachlorzyklohexanNot AvailableNot Available
gamma-LindaneNot AvailableNot Available
GammallinNot AvailableNot Available
GammaxeneNot AvailableNot Available
KwellNot AvailableNot Available
LindanNot AvailableNot Available
γ-hexachlorocyclohexaneNot AvailableNot Available
γ-HexachlorzyklohexanNot AvailableNot Available
γ-lindaneNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
GameneNot Available
KwellNot Available
ScabeneNot Available
Brand mixtures
Brand NameIngredients
Dermadex CRMBenzoic Acid + Benzyl Benzoate + Lindane + Salicylic Acid + Zinc Oxide + Zinc Undecylenate
Categories
CAS number58-89-9
WeightAverage: 290.83
Monoisotopic: 287.860066434
Chemical FormulaC6H6Cl6
InChI KeyJLYXXMFPNIAWKQ-GNIYUCBRSA-N
InChI
InChI=1S/C6H6Cl6/c7-1-2(8)4(10)6(12)5(11)3(1)9/h1-6H/t1-,2-,3-,4+,5+,6+
IUPAC Name
(1R,2S,3r,4R,5S,6r)-1,2,3,4,5,6-hexachlorocyclohexane
SMILES
Cl[C@H]1[C@H](Cl)[C@@H](Cl)[C@@H](Cl)[C@H](Cl)[C@H]1Cl
Mass Specshow(11.7 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassOrganonitrogen Compounds
ClassAmines
SubclassPolyamines
Direct parentPolyamines
Alternative parentsOrganochlorides; Alkyl Chlorides
Substituentsorganochloride; organohalogen; alkyl halide; alkyl chloride
Classification descriptionThis compound belongs to the polyamines. These are compounds containing more than one amine group.
Pharmacology
IndicationFor the treatment of patients infested with Sarcoptes scabiei or pediculosis capitis who have either failed to respond to adequate doses, or are intolerant of other approved therapies.
PharmacodynamicsScabies is a common, highly pruritic infestation of the skin caused by Sarcoptes scabiei (lice). It is a very contagious condition with specific lesions, such as burrows, and nonspecific lesions, such as papules, vesicles and excoriations. The typical areas of the body it affects are finger webs, scalp (hair), wrists, axillary folds, abdomen, buttocks, inframammary folds and genitalia (males). It is characterized by intense night-time itching. Scabies is spread through close personal contact (relatives, sexual partners, schoolchildren, chronically ill patients and crowded communities). Scabies infestations and the corresponding symptoms can be eliminated by killing the scabies with topical insecticides or scabicides. Lindane is a scabicide that is essentially an organochloride insecticide.
Mechanism of actionLindane is an organochloride insecticide that has similar neurotoxic protperties to DDT. It exerts its parasiticidal action by being directly absorbed through the parasite's exoskeleton (primarily lice, or scabies) and their ova. The gamma-aminobutyric acid (GABA(1)) receptor/chloride ionophore complex is the primary site of action for lindane, and other insecticides such as endosulfan, and fipronil. Blockage of the GABA-gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system. This results in paralysis, convulsions, and death. Lindane has very low ovicidal activity.
AbsorptionLindane is absorbed significantly through the skin. A mean peak blood concentration of 28 nanograms per mL occurred in infants and children 6 hours after total body application of lindane lotion for scabies.
Volume of distributionNot Available
Protein binding91%
Metabolism

Primarily hepatic through dechlorination leading to 2-chlorophenol, 0-chlorophenol, chlorocyclohexane, chlorocyclohexanol.

Route of eliminationNot Available
Half life18 hours
ClearanceNot Available
ToxicityLindane is a moderately toxic compound via oral exposure, with a reported oral LD50 of 88 to 190 mg/kg in rats. Gamma-HCH (which constitutes 99% of lindane) is generally considered to be the most acutely toxic of the isomers following single administration. It is moderately toxic via the dermal route as well, with reported dermal LD50 values of 500 to 1000 mg/kg in rats, 300 mg/kg in mice, 400 mg/kg in guinea pigs, and 300 mg/kg in rabbits. Acute exposure to lindane may lead to central nervous system stimulation (usually developing within 1 hour), mental/motor impairment, excitation, clonic (intermittent) and tonic (continuous) convulsion. Other adverse reactions include central nervous system toxicity, as well as skin and gastrointestinal changes.
Affected organisms
  • Scabies (Sarcoptes scabei) and other insects
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9918
Blood Brain Barrier + 0.9862
Caco-2 permeable + 0.8369
P-glycoprotein substrate Non-substrate 0.8826
P-glycoprotein inhibitor I Non-inhibitor 0.9733
P-glycoprotein inhibitor II Non-inhibitor 0.9944
Renal organic cation transporter Non-inhibitor 0.8593
CYP450 2C9 substrate Non-substrate 0.8522
CYP450 2D6 substrate Non-substrate 0.7758
CYP450 3A4 substrate Non-substrate 0.7335
CYP450 1A2 substrate Inhibitor 0.6037
CYP450 2C9 substrate Non-inhibitor 0.7892
CYP450 2D6 substrate Non-inhibitor 0.9592
CYP450 2C19 substrate Non-inhibitor 0.5936
CYP450 3A4 substrate Non-inhibitor 0.9007
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7408
Ames test Non AMES toxic 0.9754
Carcinogenicity Carcinogens 0.5058
Biodegradation Not ready biodegradable 0.9271
Rat acute toxicity 2.0905 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9077
hERG inhibition (predictor II) Non-inhibitor 0.9617
Pharmacoeconomics
Manufacturers
  • Reed and carnrick pharmaceuticals div block drug co inc
  • Sola barnes hind
  • Olta pharmaceuticals corp
  • Wockhardt eu operations (swiss) ag
  • Stiefel laboratories inc
Packagers
Dosage forms
FormRouteStrength
EmulsionTopical
LotionTopical
ShampooTopical
Prices
Unit descriptionCostUnit
Lindane 1% Lotion 60ml Bottle142.33USDbottle
Lindane 1% Shampoo 60ml Bottle142.33USDbottle
Lindane 1% lotion5.16USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Stateliquid
Experimental Properties
PropertyValueSource
melting point112.5 °CPhysProp
boiling point323.4 °CPhysProp
water solubility7.3 mg/L (at 25 °C)RICHARDSON,LT & MILLER,DM (1960)
logP3.72HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility5.47e-03 g/lALOGPS
logP3.94ALOGPS
logP4.35ChemAxon
logS-4.7ALOGPS
physiological charge0ChemAxon
hydrogen acceptor count0ChemAxon
hydrogen donor count0ChemAxon
polar surface area0ChemAxon
rotatable bond count0ChemAxon
refractivity54.08ChemAxon
polarizability23.08ChemAxon
number of rings1ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleYesChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Brown VJ: Life after lindane in California. Environ Health Perspect. 2008 Mar;116(3):A128. Pubmed
  2. Strong M, Johnstone PW: Interventions for treating scabies. Cochrane Database Syst Rev. 2007 Jul 18;(3):CD000320. Pubmed
External Links
ResourceLink
KEGG DrugD00360
KEGG CompoundC07075
ChEBI32888
ChEMBLCHEMBL15891
Therapeutic Targets DatabaseDAP001036
PharmGKBPA164754914
Drug Product Database703605
RxListhttp://www.rxlist.com/cgi/generic2/lindane.htm
Drugs.comhttp://www.drugs.com/cdi/lindane-lotion.html
WikipediaLindane
ATC CodesP03AB02D08AE01
AHFS Codes
  • 84:04.92
  • 84:04.12
PDB EntriesNot Available
FDA labelNot Available
MSDSshow(54.1 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Gamma-aminobutyric acid receptor subunit beta-1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Gamma-aminobutyric acid receptor subunit beta-1 P18505 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Cole LM, Roush RT, Casida JE: Drosophila GABA-gated chloride channel: modified [3H]EBOB binding site associated with Ala—>Ser or Gly mutants of Rdl subunit. Life Sci. 1995;56(10):757-65. Pubmed
  4. Sauviat MP, Pages N: [Cardiotoxicity of lindane, a gamma isomer of hexachlorocyclohexane] J Soc Biol. 2002;196(4):339-48. Pubmed
  5. Anand M, Agrawal AK, Rehmani BN, Gupta GS, Rana MD, Seth PK: Role of GABA receptor complex in low dose lindane (HCH) induced neurotoxicity: neurobehavioural, neurochemical and electrophysiological studies. Drug Chem Toxicol. 1998 Feb;21(1):35-46. Pubmed
  6. Joy RM, Walby WF, Stark LG, Albertson TE: Lindane blocks GABAA-mediated inhibition and modulates pyramidal cell excitability in the rat hippocampal slice. Neurotoxicology. 1995 Summer;16(2):217-28. Pubmed
  7. Bloomquist JR: Chloride channels as tools for developing selective insecticides. Arch Insect Biochem Physiol. 2003 Dec;54(4):145-56. Pubmed
  8. Narahashi T: Neuronal ion channels as the target sites of insecticides. Pharmacol Toxicol. 1996 Jul;79(1):1-14. Pubmed
  9. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
  10. Vale C, Fonfria E, Bujons J, Messeguer A, Rodriguez-Farre E, Sunol C: The organochlorine pesticides gamma-hexachlorocyclohexane (lindane), alpha-endosulfan and dieldrin differentially interact with GABA and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. Pubmed
  11. Heusinkveld HJ, Thomas GO, Lamot I, van den Berg M, Kroese AB, Westerink RH: Dual actions of lindane (gamma-hexachlorocyclohexane) on calcium homeostasis and exocytosis in rat PC12 cells. Toxicol Appl Pharmacol. 2010 Oct 1;248(1):12-9. Epub 2010 Jun 21. Pubmed

2. Glycine receptor subunit alpha-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Glycine receptor subunit alpha-1 P23415 Details

References:

  1. Vale C, Fonfria E, Bujons J, Messeguer A, Rodriguez-Farre E, Sunol C: The organochlorine pesticides gamma-hexachlorocyclohexane (lindane), alpha-endosulfan and dieldrin differentially interact with GABA and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. Pubmed
  2. Heusinkveld HJ, Thomas GO, Lamot I, van den Berg M, Kroese AB, Westerink RH: Dual actions of lindane (gamma-hexachlorocyclohexane) on calcium homeostasis and exocytosis in rat PC12 cells. Toxicol Appl Pharmacol. 2010 Oct 1;248(1):12-9. Epub 2010 Jun 21. Pubmed

3. Glycine receptor subunit alpha-2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Glycine receptor subunit alpha-2 P23416 Details

References:

  1. Vale C, Fonfria E, Bujons J, Messeguer A, Rodriguez-Farre E, Sunol C: The organochlorine pesticides gamma-hexachlorocyclohexane (lindane), alpha-endosulfan and dieldrin differentially interact with GABA and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. Pubmed
  2. Heusinkveld HJ, Thomas GO, Lamot I, van den Berg M, Kroese AB, Westerink RH: Dual actions of lindane (gamma-hexachlorocyclohexane) on calcium homeostasis and exocytosis in rat PC12 cells. Toxicol Appl Pharmacol. 2010 Oct 1;248(1):12-9. Epub 2010 Jun 21. Pubmed

4. Glycine receptor subunit alpha-3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Glycine receptor subunit alpha-3 O75311 Details

References:

  1. Vale C, Fonfria E, Bujons J, Messeguer A, Rodriguez-Farre E, Sunol C: The organochlorine pesticides gamma-hexachlorocyclohexane (lindane), alpha-endosulfan and dieldrin differentially interact with GABA and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. Pubmed
  2. Heusinkveld HJ, Thomas GO, Lamot I, van den Berg M, Kroese AB, Westerink RH: Dual actions of lindane (gamma-hexachlorocyclohexane) on calcium homeostasis and exocytosis in rat PC12 cells. Toxicol Appl Pharmacol. 2010 Oct 1;248(1):12-9. Epub 2010 Jun 21. Pubmed

5. Glycine receptor subunit beta

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Glycine receptor subunit beta P48167 Details

References:

  1. Vale C, Fonfria E, Bujons J, Messeguer A, Rodriguez-Farre E, Sunol C: The organochlorine pesticides gamma-hexachlorocyclohexane (lindane), alpha-endosulfan and dieldrin differentially interact with GABA and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. Pubmed
  2. Heusinkveld HJ, Thomas GO, Lamot I, van den Berg M, Kroese AB, Westerink RH: Dual actions of lindane (gamma-hexachlorocyclohexane) on calcium homeostasis and exocytosis in rat PC12 cells. Toxicol Appl Pharmacol. 2010 Oct 1;248(1):12-9. Epub 2010 Jun 21. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on May 20, 2014 11:55