DT-Web

DB00431 - Lindane


Identification
Name Lindane
Accession Number DB00431 (APRD01072)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 290.83
Groups approved
Monoisotopic Weight 287.860066434
Pharmacology
Indication For 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.
Mechanism of action Lindane 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.
Absorption Lindane 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.
Protein binding 91%
Biotransformation Primarily hepatic through dechlorination leading to 2-chlorophenol, 0-chlorophenol, chlorocyclohexane, chlorocyclohexanol.
Route of elimination Not Available
Toxicity Lindane 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
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Gamma-aminobutyric-acid receptor subunit beta-1
Name Gamma-aminobutyric-acid receptor subunit beta-1
Gene Name GABRB1
Pharmacological action yes
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
  • Sauviat MP, Pages N: [Cardiotoxicity of lindane, a gamma isomer of hexachlorocyclohexane] J Soc Biol. 2002;196(4):339-48. - Pubmed
  • 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
  • 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
  • Bloomquist JR: Chloride channels as tools for developing selective insecticides. Arch Insect Biochem Physiol. 2003 Dec;54(4):145-56. - Pubmed
  • Narahashi T: Neuronal ion channels as the target sites of insecticides. Pharmacol Toxicol. 1996 Jul;79(1):1-14. - Pubmed
  • 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
  • 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(A) and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. - Pubmed
  • 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
DTHybrid score 0.2566
Glycine receptor subunit alpha-1
Name Glycine receptor subunit alpha-1
Gene Name GLRA1
Pharmacological action unknown
Actions antagonist
References
  • 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(A) and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. - Pubmed
  • 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
DTHybrid score 0.4067
Glycine receptor subunit alpha-2
Name Glycine receptor subunit alpha-2
Gene Name GLRA2
Pharmacological action unknown
Actions antagonist
References
  • 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(A) and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. - Pubmed
  • 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
DTHybrid score 0.4745
Glycine receptor subunit alpha-3
Name Glycine receptor subunit alpha-3
Gene Name GLRA3
Pharmacological action unknown
Actions antagonist
References
  • 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(A) and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. - Pubmed
  • 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
DTHybrid score 0.4946
Glycine receptor subunit beta
Name Glycine receptor subunit beta
Gene Name GLRB
Pharmacological action unknown
Actions antagonist
References
  • 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(A) and glycine-gated chloride channels in primary cultures of cerebellar granule cells. Neuroscience. 2003;117(2):397-403. - Pubmed
  • 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
DTHybrid score 0.3941

Predictions


Id Partner name Gene Name Score
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.1578
142 Gamma-aminobutyric-acid receptor subunit rho-1 GABRR1 0.1164
4099 Gamma-aminobutyric-acid receptor subunit beta-3 GABRB3 0.0901
3426 Glutamine synthetase glnA 0.0801
3987 Glutamine synthetase GLUL 0.0801
4100 Gamma-aminobutyric-acid receptor subunit beta-2 GABRB2 0.0768
6086 Gamma-aminobutyric acid receptor subunit gamma-2 GABRG2 0.0693
241 Calcium-transporting ATPase type 2C member 1 ATP2C1 0.0681
537 ATP synthase delta chain, mitochondrial ATP5D 0.0671
6087 Gamma-aminobutyric acid receptor subunit gamma-1 GABRG1 0.0629
6093 Gamma-aminobutyric acid receptor subunit delta GABRD 0.0628
6089 Gamma-aminobutyric acid receptor subunit epsilon GABRE 0.0626
705 Glutamate receptor 1 GRIA1 0.0614
559 NADH-ubiquinone oxidoreductase chain 1 MT-ND1 0.0613
6024 Cytochrome P450 1A1 CYP1A1 0.0594
6088 Gamma-aminobutyric acid receptor subunit gamma-3 GABRG3 0.0578
6090 Gamma-aminobutyric acid receptor subunit pi GABRP 0.0578
6092 Gamma-aminobutyric acid receptor subunit rho-2 GABRR2 0.0577
6115 Gamma-aminobutyric acid receptor subunit rho-3 GABRR3 0.0577
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0549
4512 Cytochrome P450 3A4 CYP3A4 0.0537
4058 Glycine N-acyltransferase-like protein 2 GLYATL2 0.0493
4059 Glycine N-acyltransferase-like protein 1 GLYATL1 0.0493
4057 Glycine N-acyltransferase GLYAT 0.0493
4056 N-arachidonyl glycine receptor GPR18 0.0493
4060 Vesicular inhibitory amino acid transporter SLC32A1 0.0493
4055 Bile acid CoA:amino acid N-acyltransferase BAAT 0.0493
4061 Peroxisomal sarcosine oxidase PIPOX 0.0493
1466 Glycyl-tRNA synthetase GARS 0.0493
1088 5-aminolevulinate synthase, erythroid-specific, mitochondrial ALAS2 0.0493
1236 Sodium- and chloride-dependent glycine transporter 1 SLC6A9 0.0493
4062 Sodium- and chloride-dependent glycine transporter 2 SLC6A5 0.0493
523 Gamma-aminobutyric-acid receptor subunit alpha-5 GABRA5 0.049
580 Gamma-aminobutyric-acid receptor subunit alpha-3 GABRA3 0.049
423 Gamma-aminobutyric-acid receptor subunit alpha-2 GABRA2 0.0486
6013 Cytochrome P450 2E1 CYP2E1 0.0441
575 2-amino-3-ketobutyrate coenzyme A ligase, mitochondrial GCAT 0.0388
455 5-aminolevulinate synthase, nonspecific, mitochondrial ALAS1 0.0388
681 Glycine dehydrogenase [decarboxylating], mitochondrial GLDC 0.0388
6151 Monocarboxylate transporter 10 SLC16A10 0.038
6030 Cytochrome P450 2B6 CYP2B6 0.0366
591 Glutamate [NMDA] receptor subunit 3B GRIN3B 0.0359
4054 Glycine cleavage system H protein, mitochondrial GCSH 0.0358
6091 Gamma-aminobutyric acid receptor subunit theta GABRQ 0.0352
5469 Head decoration protein shp 0.035
3884 SHMT2 protein SHMT2 0.0347
3901 SHMT2 protein SHMT2 0.0347
3885 Hypothetical protein DKFZp686P09201 DKFZp686P09201 0.0347
3879 Serine hydroxymethyltransferase 2 Not Available 0.0347
321 Serine hydroxymethyltransferase, mitochondrial SHMT2 0.0347
114 Alanine--glyoxylate aminotransferase 2, mitochondrial AGXT2 0.0339
207 Glutathione synthetase GSS 0.0335
5269 Glutathione synthetase gshB 0.0335
411 Glycine N-methyltransferase GNMT 0.0335
837 Glutamate [NMDA] receptor subunit epsilon-1 GRIN2A 0.033
587 Serum albumin ALB 0.0327
505 Glutamate [NMDA] receptor subunit epsilon-3 GRIN2C 0.0326
383 Glycine amidinotransferase, mitochondrial GATM 0.0318
349 Serine--pyruvate aminotransferase AGXT 0.0301
593 Proton-coupled amino acid transporter 1 SLC36A1 0.03
4757 Cytochrome P450 2C9 CYP2C9 0.0297
530 Gamma-aminobutyric-acid receptor subunit alpha-4 GABRA4 0.029
367 Serine hydroxymethyltransferase, cytosolic SHMT1 0.0286
841 Gamma-aminobutyric-acid receptor subunit alpha-6 GABRA6 0.0272
251 Alcohol dehydrogenase 1A ADH1A 0.026
471 Sodium- and chloride-dependent neutral and basic amino acid transporter B(0+) SLC6A14 0.025
1588 Multidrug resistance protein 1 ABCB1 0.0235
811 Translocator protein TSPO 0.0231
444 Alcohol dehydrogenase 1B ADH1B 0.0226
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0224
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0219
862 Multidrug resistance-associated protein 1 ABCC1 0.0218
468 Cytochrome P450 4A11 CYP4A11 0.0214
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0205
6016 Cytochrome P450 2C19 CYP2C19 0.0202
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0199
517 Alcohol dehydrogenase 1C ADH1C 0.0192
4200 Cytochrome P450 1A2 CYP1A2 0.0171
610 Calcium-activated potassium channel subunit alpha 1 KCNMA1 0.015
5718 Cytochrome P450 2A6 CYP2A6 0.0148
2981 Phospholipase A2, membrane associated PLA2G2A 0.0145
489 Monocarboxylate transporter 2 SLC16A7 0.0121
500 Monocarboxylate transporter 4 SLC16A3 0.0118
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0105
738 Monocarboxylate transporter 1 SLC16A1 0.0104
465 Calmodulin CALM1 0.008
1768 Guanine nucleotide-binding protein G(I)/G(S)/G(O) gamma-2 subunit GNG2 0.0079
1268 Neuropeptide S receptor NPSR1 0.0079
1571 G protein-activated inward rectifier potassium channel 1 KCNJ3 0.0079
1581 G protein-activated inward rectifier potassium channel 2 KCNJ6 0.0079
4119 Cytochrome P450 2D6 CYP2D6 0.007
6073 Potassium channel subfamily K member 9 KCNK9 0.0063
6072 Potassium channel subfamily K member 3 KCNK3 0.0063
6107 Cytochrome P450 3A7 CYP3A7 0.0059
4118 Cytochrome P450 3A5 CYP3A5 0.0056
462 Intermediate conductance calcium-activated potassium channel protein 4 KCNN4 0.0052
6106 Cytochrome P450 2C18 CYP2C18 0.0052
2207 Rhodopsin RHO 0.0044
4924 Cytochrome P450 2C8 CYP2C8 0.0032
276 Sodium- and chloride-dependent GABA transporter 1 SLC6A1 0.0026
6102 Arylamine N-acetyltransferase 2 NAT2 0.0026
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0024
6031 Cytochrome P450 3A43 CYP3A43 0.002
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0019
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0017
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0016
6144 Solute carrier family 22 member 2 SLC22A2 0.0015
6145 Solute carrier family 22 member 1 SLC22A1 0.0013
20 Prostaglandin G/H synthase 1 PTGS1 0.0011
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