PK-11195 REDUCES THE BRAIN AVAILABILITY OF LINDANE IN RATS AND THE CONVULSIONS INDUCED BY THIS NEUROTOXIC AGENT

The effect of pretreatment with PK 11195, a ligand of the 'peripheral- type' benzodiazepine receptor (PER), on convulsions induced by lindane (gamma-hexachlorocyclohexane, gamma-HCH) in rats was examined, to det ermine whether the mechanism of this convulsant activity may be mediat ed through the PER. PK 11195 elicited a protective effect against the convulsant activity of orally administered lindane. It reduced the fre quency of animals exhibiting convulsions and delayed the time to onset of these seizures. The concentration of lindane in the brain was foun d to be significantly lower in PK 11195 pretreated rats and a high cor relation between blood and brain lindane concentrations was obtained. When similar experiments were repeated with alpha-HCH, a non-convulsan t isomer of HCH, brain and blood concentrations were again found to be significantly reduced in PK 11195 pretreated animals. We conclude tha t the 'anticonvulsant' action of PK 11195 was not due to an interactio n 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.