Lindane cyclodienes

The biggest exception to this, of course, is the GABA system which is associated with a variety of active drugs. Besides the older picrotoxinin (I) and bicuculline (II), there are barbiturates (III), nipecotic acid (IV), muscimol (V), benzodiazepines (VI), baclofen (VIII), and avermectins to guide the search for active leads. The recent suggestion of similarities in structure and mode of action of lindane, cyclodienes and picrotoxinin analogs (J ) throws open even more possibilities. 

Mode of Motion. The cyclodienes, like lindane and toxaphene, affect the nerve axon produciag hyperactivity, convulsions, prostration, and death. The biochemical lesion is the competitive inhibition of the y-aminobutyric acid (GABA) neurotransmitter binding site of the nerve axon. Spray workers with lengthy exposure to dieldrin have suffered from prolonged and repeated central nervous system disturbances produciag epileptiform coavulsioas. Similar disturbances occurred ia workers heavily exposed to chlordecoae. 

Lindane is one of eight different hexachlorocyclohexane (HCH), C H Cl, isomers and its Chemical Abstract n.2cniQ is la, 2a 3P, 4a, 5a 6P-hexachlorocyclohexane [58-89-9] (y-HCH or y-BHC, ben2ene hexachloride) (80). Commercial products containing lindane are marketed as either a mixture of isomers or as the pure y-BHC isomer. Not unexpectedly, lindane is a highly stable lipophilic compound and it has been used extensively worldwide as an insecticide. In contrast, hexachloropentadiene, C Cl, is an extremely reactive industrial intermediate used as a chemical intermediate in the synthesis of a broad range of cyclodiene-derived pesticides, which include endosulfan, endrin, heptachlor, and several different organohalogen flame retardants (81). 

Lawrence, L.J and Casida, J.E (1984). Interactions of lindane, toxaphene, and cyclodienes with brain-specific t-bntyl phosphorothionate receptor. Life Science 35, 171. 

Cyclodiene pesticides, of which endrin and its oxidized analogs are representative, can also be estimated by receptor-assay technique. Cyclodiene pesticides exert their mode of action by altering central nervous system membrane ion transport. In work reported by Saleh et al. (1993), a labeled amino acid, GABA, that binds to the chloride channel receptor is displaced by endrin (and other similar molecules), and thus serves as an assay for these pesticides. The GABA receptor was shown to be a potentially useful biomarker for organochlorine pesticides such as lindane, toxaphene, endrin, chlordane, and others. The assay involves small quantities of blood (0.1 mL), and requires only that the plasma be separated from the... 

Other chemicals are agonists such as those that directly affect the y-butyric acid receptor (GABAa) receptor in neurons. Drugs such as barbiturates and benzodiazepines are agonists (activators) for this receptor and cause neuronal inhibition and sedation at therapeutic doses but coma and depression at higher doses. Conversely, antagonists (inhibitors) for this receptor such as the insecticides lindane and cyclodienes and picrotoxin inhibit neurons and may cause tremor and convulsions at toxic doses. 

Alachlor, Benzene hexachloride. Cyclodienes Aldrin, Chlordane, Dieldrin, Endrin, Endosulfan, Heptachlor, Isodrin, Telodrin and Toxaphene, DDT and metabolites, Dicofol, Dimethoate, Lindane, Methoxychlor, Mirex, Pentachlorophenol, Perthane... 

Resistance to the cyclodienes was evident by this time and was known to extend to lindane and toxaphene but not to DDT. 

Lindane is relatively non-persistent, especially under anaerobic conditions, and although its more highly chlorinated residues may present the same problems as those of polychlorophenols, the less chlorinated residues should follow pathways similar to those established for the microbial degradation of the chlorinated phenoxyalkanoic acid herbicides. Recent evidence (46) indicates that certain microbes can dechlorinate DDT anaerobically, thereby making available intermediates which may undergo further aerobic attack, leading in principle to total degradation. The ultimate fate of the hexachloronorbornene nucleus of cyclodienes is still uncertain and this question continues to attract attention. 

Soloway (6l) suggested that the cyclodienes and lindane have in common two electronegative centres separated by a similar distance and pointed out the similarity between the profiles of these molecules viewed perpendicular to their plane of symmetry. 

The resemblance between lindane and the cyclodiene structure is particularly striking if one compares models of lindane and the photoisomer of the molecule SD (Figure 8), in which the S-chlorine is replaced by hydrogen and the usual double bond is absent ... 

GABA-gated chloride channels Cyclodienes, lindane, phenylpyrazoles, Avermectins, emamectin benzoate, milbemectin Antagonism Chloride channel activators... 

Symptomatology is essentially the same as that described for organochlorine insecticides. In many cases, convulsions are the first sign of toxicity without the progression of nerve hyperactivity seen in other classes of organochlorine insecticides. More recently, evidence of endocrine disruption in both mammalian and other species has been accumulating for several cyclodiene pesticides including chlordane, aldrin, dieldrin, lindane, and endosulfan. 

Organochlorine insecticides may be divided into three broad groups dichlorodiphenylethanes, such as DDT and methoxychlor cyclodienes, such as chlor-dane and dieldrin and hexachlorocyclohexanes, such as lindane. Mirex and chlordecone, however, are organochlorine insecticides whose caged structures do not fit well into the previous groups. 

Benomyi/Carbendazim Carbofuran Chlorothalonil Chlorpyrifos Cyanazine Cyclodienes Methomyl Metolachlor Procymidone Simazine Spinosad Triclopyr DDT Lindane Toxaphene Triazines Industrial contaminants/remediation BTEX PAHs, cPAHs PCBs PCP TPH TNT RDX... 

Some older compounds such as toxaphene, lindane and cyclodiene insecticides have been around for some time without their mode of action being known. My third observation is that, almost as a tradition, some insecticidal activity has been found and then later a physiological lesion has been discovered. The initial acaricidal activity of chlordimeform, the nematicidal activity of avermectin, or the diptericidal activity of cyromazine are good examples. 

Recent studies have grouped lindane with the cyclodienes on the basisLjaf its potent and stereospecific inhibition of [3H]DHPTX (.2,3) and [3DS]TBPS (4 J>) binding. However, the quantitative correlations between potency in the chloride flux assay, potency in the [3 >S]TBPS binding assay, and acute toxicity that were observed for the cyclodienes do not extend to lindane. Lindane was a very weak inhibitor of chloride uptake (I 1 mM J7). Inclusion of the data... 

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