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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

gamma-Hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to be a seizure-inducing agent in mammals. gamma-HCH and two non-convulsant isomers of HCH (alpha and delta) were compared as to their CNS-related pharmacological and biochemical effects. gamma-HCH was a potent seizure-inducing agent in mice while the alpha or the delta isomer significantly decreased mouse motor activity. Acute administration of gamma-HCH increased the severity of seizure activity of either pentylenetetrazol (PTZ) or picrotoxin (PIC). However, acute exposure to alpha- or delta-HCH inhibited the seizure activity due to PTZ but increased that of PIC. gamma-, alpha-, and delta-HCH inhibited the binding of 3H-TBOB (a ligand for the GABA-A receptor linked chloride channel) to mouse whole brain membranes with IC50 values of 4.6, 20.0, and 31.8 microM, respectively. All three isomers were weak inhibitors of GABA-stimulated uptake of 36Cl into mouse brain neurosynaptosome preparations in vitro, being much less potent than PIC, an agent known to act at the chloride channel. At concentrations producing no effect by itself, gamma-HCH increased the effect of PIC on GABA-stimulated chloride uptake. In combination with PTZ, the delta and alpha isomers decreased the effect of PTZ in vitro while the gamma isomer increased the effects of PTZ. These effects correspond to observations made on seizure activity. The results show that the non-seizure-inducing isomers of HCH have biochemical and pharmacological effects in the CNS which differ from those of the insecticidally relevant gamma isomer. The actions of the HCH isomers in the CNS appear to be mediated, at least in part, through GABA-A receptor linked chloride channel sites.
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PMID:CNS biochemical and pharmacological effects of the isomers of hexachlorocyclohexane (lindane) in the mouse. 245 20

Lindane (gamma-hexachlorocyclohexane) is an organochlorine insecticide with known neurotoxic effects. Its mechanism of action is not well understood although it has been proposed that lindane acts as a non-competitive antagonist at the gamma-aminobutyric acid (GABA)-A receptor. We studied the effect of lindane (150 mg/kg) on the GABAergic and dopaminergic systems by measuring the concentration of GABA, dopamine and its metabolites in 7 brain areas at the onset of seizures. All animals suffered tonic convulsions at 18.3 +/- 1.4 min after lindane administration. The concentration of GABA was only slightly but significantly decreased in the colliculi without modifications in the other areas. The concentration of dopamine was increased in the mesencephalon and that of its metabolite DOPAC was also increased in the mesencephalon and the striatum.
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PMID:Convulsant effect of lindane and regional brain concentration of GABA and dopamine. 245 42

Lindane-induced dose- and time-related changes in regional 2-14C-deoxyglucose (2-DG) uptake were examined in 59 discrete rat brain structures using the 2-DG autoradiographic technique. At different times (0.5-144 hr) after administration of a seizure-inducing single dose of lindane (60 mg/kg), 2-DG uptake was significantly increased in 18 cortical and subcortical regions mainly related to the limbic system (e.g., Ammon's horn, dentate gyrus, septal nuclei, nucleus accumbens, olfactory cortex) and extrapyramidal and sensory-motor areas (e.g., cerebellar cortex, red nucleus, medial vestibular nucleus). There was also a significant increase in superior colliculus layer II. In addition, significant decreases occurred in a group of 6 regions (e.g., auditory and motor cortices). Non-convulsing animals treated with the same dose of lindane showed a regional pattern of 2-DG uptake less modified than the convulsant group. A non-convulsant single dose of lindane (30 mg/kg) also modified significantly the 2-DG uptake (0.5-24 hr) in some brain areas. Although the various single doses of lindane tested produced different altered patterns of brain 2-DG uptake, some structures showed a similar trend in their modification (e.g., superior colliculi and accumbens, raphe and red nuclei). Repeated non-convulsant doses of lindane produced defined and long-lasting significant elevations of 2-DG uptake in some subcortical structures (e.g., dorsal cochlear nucleus, dentate gyrus). Considering the treated groups all together, 2-DG uptake increased significantly in 26 of the 59 regions examined but only decreased significantly in 9 of them during the course of lindane effects. This fact can be related to the stimulant action described for this neurotoxic agent. The observed pattern provides a descriptive approach to the functional alterations occurring in vivo during the course of lindane intoxication. These results may be linked to the proposed mechanism of lindane neurotoxicity postulating an initial action on the GABAA receptor-chloride channel sites.
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PMID:Regional changes in brain 2-14C-deoxyglucose uptake induced by convulsant and non-convulsant doses of lindane. 248 96

Neonatal male rats were exposed to lindane or corn oil directly by gavage or indirectly by maternal exposure. All surviving offspring were implanted with amygdaloid electrodes 90 days after weaning. Amygdaloid kindling began 10 days later using standard procedures. Neonatal lindane-exposed rats kindled significantly faster (9.9 +/- 0.5 days) than control groups (11.2 +/- 0.5 days). Lindane-exposed rats tended to have longer and more severe seizures than did non-exposed rats on each trial during kindling acquisition. These findings demonstrate that high exposures of lindane during development can lead to enduring changes in the nervous system that facilitate adult kindling.
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PMID:Facilitation of kindling in adult rats following neonatal exposure to lindane. 258 Jun 1

Rats receiving daily oral administrations of lindane were kindled using daily amygdaloid stimulation. In naive rats lindane exposure increased the probability of evoking an afterdischarge and increased the probability that a convulsive response would be associated with the afterdischarge. During kindling lindane increased the rate of acquisition of the fully kindled state. Lindane exposed rats required fewer stimulations, fewer afterdischarges and fewer seconds of afterdischarge to kindle. The final kindled state, however, was not modified by lindane exposure. The effects of lindane on kindling were directly proportional to exposure. A log-linear regression of the data estimated the minimal effective exposure level to be about 0.5 mg/kg/day lindane. Brain concentrations at this exposure were about 0.5 microgram/g, while blood levels were near 0.1 microgram/ml. The kindled seizure model appears to be a useful tool for estimating exposures at which certain neurotoxic responses emerge.
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PMID:Proconvulsant effects of lindane: enhancement of amygdaloid kindling in the rat. 617 84

The neurochemical changes underlying the convulsant effects of Lindane, an organochlorinated insecticide, are not known. Since electrophysiological and pharmacological data suggest the view that gamma-aminobutyric acid (GABA) plays an important role in controlling convulsive seizures, the effect of lindane on the GABAergic system, on different areas of the rat brain, has been evaluated. Lindane (100 mg/kg i.p.) induces a selective increase of GABA levels in the cerebellum after the onset of seizures. Non-significant increases were observed in the cortex and hippocampus. GABA turnover, as measured by the accumulation rate of GABA after blockade of its catabolism, was increased in all the brain areas examined. On the other hand, lindane does not significantly displace from their binding sites in vitro either 3H-GABA or 3H-Flunitrazepam. These findings show that convulsions elicited by lindane are not due to an impairment of the GABAergic system. Moreover, an increase of GABA functional activity takes place, in all brain areas examined, probably as a protective mechanism to counteract the seizures.
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PMID:Convulsions induced by lindane and the involvement of the GABAergic system. 619 70

Daily exposure to lindane, 5 mg/kg, produced a number of consistent changes in rats undergoing amygdaloid kindling. Lindane decreased the number of afterdischarge-evoking stimulations required to produce the fully kindled state, increased the length of each successive afterdischarge during kindling and increased the severity of each convulsive response during kindling. However, lindane exposure did not change the total seconds of afterdischarge activity required to create the fully kindled state. In this study the enhancement of kindling rates by lindane stemmed primarily from an increase in the duration of epileptiform activity following each amygdaloid stimulation. These proconvulsant effects cannot be attributed to a lowering of seizure thresholds by lindane. Thresholds evaluated at different times during and after completion of kindling were either unaffected or actually elevated by lindane exposure. The length and severity of seizures evoked in fully kindled subjects by amygdaloid stimulation were much less affected by lindane exposure. This indicates that the most useful period for demonstrating proconvulsant activity with the kindling seizure model is during the dynamic phase of seizure development. Once the process has reached completion, seizures are maximally expressed, and their duration is controlled by processes not as susceptible to lindane exposures.
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PMID:Proconvulsant actions of lindane: effects on afterdischarge thresholds and durations during amygdaloid kindling in rats. 619 65

Scabies is a common infestation for patients of all ages throughout the world. One of the standard therapies for scabies is 1% lindane lotion. Lindane has been associated with neurotoxic reactions, specifically seizures. We describe a case of a middle-aged adult man with human immunodeficiency virus (HIV) infection who was found to have typical scabies and was treated with a single topical application of lindane. Two hours after the application, the patient experienced a new-onset generalized seizure. We believe that the triad of HIV infection, medications that reduce seizure thresholds, and percutaneous absorption factors, in the aggregate, induced the seizure. We believe that lindane should not be prescribed for patients with HIV infection.
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PMID:Neurotoxic reaction to lindane in an HIV-seropositive patient. An old medication's new problem. 753 5

Lindane and endosulfan are chlorinated hydrocarbon pesticides that bind to the gamma-aminobutyric-acidA (GABAA) receptor ionophore complex. We have previously demonstrated development of a persistent predisposition to the seizure-inducing properties of these pesticides following repeated administration of initially subconvulsive doses. A subsequent facilitation of electrical kindling development indicated that a chemical kindling mechanism may contribute to this enhanced sensitivity. We tested the bidirectionality of kindling transfer induced by chemical and electrical means by comparing the convulsive thresholds of lindane and endosulfan in electrically kindled and nonkindled animals. Amygdala kindled, implanted/nonstimulated, and nonimplanted controls were administered 0, 5, 10, or 20 mg/kg of lindane or endosulfan in corn oil by gavage, and each animal's behavior was scored for the presence of myoclonic jerks (MCJ) and clonic seizures. Dose-related increases in the number of animals displaying convulsions in response to both of these pesticides were observed. The dose of lindane (4.5 mg/kg) and endosulfan (4.3 mg/kg) producing MCJs in 50% of the animals (ED50) was reduced by more than 60% in kindled animals relative to controls. A second experiment evaluated the generalized seizure threshold in previously kindled animals treated with low doses of endosulfan (0, 2.5, and 5 mg/kg, po by gavage). Endosulfan reduced the intensity of electrical stimulation required to evoke seizures in amygdala kindled animals. These data indicate that these chlorinated hydrocarbon insecticides reduce seizure thresholds in amygdala-kindled animals with acute administration, and together with previous findings (see ref. 20) demonstrate bidirectional transfer between chemical and electrical kindling.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Seizure thresholds in kindled animals are reduced by the pesticides lindane and endosulfan. 753 98

Lindane has been reported to cause central nervous system (CNS) toxicity including seizures after prolonged dermal contact and also after acute ingestions. Despite safer alternatives, lindane still remains a commonly used agent in the treatment of scabies and pediculosis. We present three cases of acute toxicity after the inadvertent oral administration of lindane in three siblings. A 17-month-old female suffered a single seizure. A 3-year-old male was listless, nauseated, pale, and had decreased responsiveness to verbal and tactile stimulation. A 4-year-old female became nauseated and required bag-valve-mask ventilation for hypoventilation. The three patients all recovered without sequelae.
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PMID:Acute lindane poisoning in three children. 1064 38


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