Neuropharmacological effects of isomers of hexachlorocyclohexane—3. An account of the convulsant activity of the γ-isomer in rats

Stein, Keith L.; Portig, J.; Noack, G.

doi:10.1016/0028-3908(81)90090-3

Cited by 17 publications

(2 citation statements)

References 27 publications

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“…Pharmacological studies with high doses of HCH show altered muscle tremors, convulsions, electroencephalogramme modification and somatomotor or somato-sensitive response in mammals (Hanig et al 1976;Stein et al 1981;Joy 1982). Recent studies on rat brain synaptosomes suggested HCH interaction with GABAergic neurotransmission (Stein et al 1981) with picrotoxin receptor (Matsumura & Ghiasuddin 1983) and increases the Ca++-uptake (Narbonne & Lievrmont 1983) establishing a link between lindane and Ca+ + equilibrium.…”

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confidence: 99%

Effects of Hexachlorocyclohexane (HCH) on the Contractile Response Induced by Norepinephrine in the Rat Isolated Vas deferens

Gandhi

Venkatakrishna‐Bhatt

1989

Pharmacology & Toxicology

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Effects of hexachlorocyclohexane (Technical HCH) on the contractile responses of rat isolated Vas deferens to norepinephrine (NE) were investigated by varying the Ca++ and Mg++ concentrations of the incubation medium. Preparations incubated in excess Ca++ (4.2 mM) or in Ca++-free Krebs solution showed decrease in sensitivity to NE. The inhibitory action of HCH reduced the sensitivity and decreased maximum responses to NE in any Mg++ concentration of the medium. In the normal Ca++ and its deficient medium decrease in sensitivity to HCH and the relevant maximum response to NE were observed. In excess Ca++, the HCH effect depressed corresponding to its maximal response to NE. The presence of EDTA depressed the HCH effect irrespective of the Ca++ influence on the receptors.

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confidence: 99%

Effects of Hexachlorocyclohexane (HCH) on the Contractile Response Induced by Norepinephrine in the Rat Isolated Vas deferens

Gandhi

Venkatakrishna‐Bhatt

1989

Pharmacology & Toxicology

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“…Lindane (y-hexachlorocyclohexane) is a polychlorocycloalkane insecticide and ectoparasiticide (Smith, 1991) that when administered to mammals causes hyperexcitability and convulsions (Stein et al, 1981;Tusell et al, 1987). This action may be related to GABAergic neurotransmission since lindane has been shown to affect the picrotoxinin (PTX) binding site associated with the chloride channel of the GABA, receptor complex (Lawrence and Casida, 1984;Abalis et al, 1985;Eldefrawi and Eldefrawi, 1987;Llorens et al, 1990;PomCs et al, 1993).…”

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confidence: 99%

Lindane cytotoxicity in cultured neocortical neurons is ameliorated by GABA and flunitrazepam

Pomés

Frandsen²,

Suñol³

et al. 1994

J of Neuroscience Research

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The effect of lindane (gamma-hexachlorocyclohexane) on [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding and GABA-stimulated 36Cl- influx was investigated in cultured cerebral cortical neurons. In addition, the cytotoxic action of lindane as well as a protection by GABA and flunitrazepam were studied together with the ability of lindane to increase the intracellular concentration of free Ca2+. Lindane was found to be toxic to the neurons, an effect that could be completely prevented by the simultaneous presence of GABA (0.1 microM) and flunitrazepam (100 microM) and reduced by GABA alone. An interaction with the GABA receptor-gated chloride channel was demonstrated by an inhibitory action of lindane on [35S]TBPS binding (IC50 188 +/- 51 nM) and on GABA-stimulated 36Cl- influx in the neurons. Lindane only marginally increased the intracellular Ca2+ concentration in the neurons. It is concluded that the cytotoxic action of lindane is mediated through interaction with GABA receptors in a manner essentially independent of changes in intracellular Ca2+ homeostasis.

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Relationship between lindane concentration in blood and brain and convulsant response in rats after oral or intraperitoneal administration

et al. 1987

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The relationships between brain and blood concentrations of lindane and its convulsant effects have been studied in rats after different po and ip doses. A good correlation was observed between dose and the frequency and time to onset of tonic seizures, the intensity of the response and lethality. An oral ED50 (84 mg/kg) and an ip ED50 (131 mg/kg) for the half-maximal incidence rate of lindane-induced tonic seizures was determined. The incidence of response was directly proportional to the log of lindane concentration in brain and blood, with an EC50 of 5.3 micrograms/g and 1.5 micrograms/ml, respectively. The threshold concentration of lindane eliciting tonic seizures was estimated to be approximately 5 micrograms/g in brain and approximately 1.5 micrograms/ml in blood. The kinetics of lindane in brain and blood were examined after a single 60 mg/kg po or ip dose over a period from 5 min to 1 week. Concentrations of lindane in brain and blood were found to be highly correlated.

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Neuropharmacological effects of isomers of hexachlorocyclohexane—3. An account of the convulsant activity of the γ-isomer in rats

Cited by 17 publications

References 27 publications

Effects of Hexachlorocyclohexane (HCH) on the Contractile Response Induced by Norepinephrine in the Rat Isolated Vas deferens

Effects of Hexachlorocyclohexane (HCH) on the Contractile Response Induced by Norepinephrine in the Rat Isolated Vas deferens

Lindane cytotoxicity in cultured neocortical neurons is ameliorated by GABA and flunitrazepam

Relationship between lindane concentration in blood and brain and convulsant response in rats after oral or intraperitoneal administration

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