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PK 11195 reduces the brain availability of lindane in rats and the convulsions induced by this neurotoxic agent.

Abstract
The effect of pretreatment with PK 11195, a ligand of the 'peripheral-type' benzodiazepine receptor (PBR), on convulsions induced by lindane (gamma-hexachlorocyclohexane, gamma-HCH) in rats was examined, to determine whether the mechanism of this convulsant activity may be mediated through the PBR. PK 11195 elicited a protective effect against the convulsant activity of orally administered lindane. It reduced the frequency of animals exhibiting convulsions and delayed the time to onset of these seizures. The concentration of lindane in the brain was found to be significantly lower in PK 11195 pretreated rats and a high correlation between blood and brain lindane concentrations was obtained. When similar experiments were repeated with alpha-HCH, a non-convulsant isomer of HCH, brain and blood concentrations were again found to be significantly reduced in PK 11195 pretreated animals. We conclude that the 'anticonvulsant' action of PK 11195 was not due to an interaction of PK 11195 and lindane on common CNS target sites, but by an action of PK 11195 on the gastrointestinal tract of the animal, delaying the absorption of lindane into the bloodstream.
AuthorsD M Zisterer, C Suñol, P N Moynagh, D C Williams, E Rodríguez-Farré
JournalLife sciences (Life Sci) Vol. 57 Issue 25 Pg. 2359-64 ( 1995) ISSN: 0024-3205 [Print] Netherlands
PMID7491094 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Isoquinolines
  • Receptors, GABA-A
  • Hexachlorocyclohexane
  • PK 11195
Topics
  • Animals
  • Biological Availability
  • Brain (metabolism)
  • Hexachlorocyclohexane (pharmacokinetics, toxicity)
  • Isoquinolines (pharmacology)
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A (physiology)
  • Seizures (chemically induced, prevention & control)

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