2166659

Folates: epileptogenic effects and enhancing effects on [3H]TBOB binding to the GABAA-receptor complex.

Article date: 1990/4/1

PubMed ID: 2166659

Journal name: Epilepsy research (ISSN: 0920-1211)

ABSTRACT

The biochemical mechanism responsible for the convulsive effects of folates was investigated. The epileptogenic effects of folates were determined in vivo by quantification of the seizures following intracortical application in rats. The rank order of epileptogenic effects is: folic acid greater than or equal to 5-HCO-H4 folate greater than H2 folate greater than 5-CH3-H4 folate. This sequence of epileptogenicity in vivo is compared to the rank order of the effects of folates on radioligand binding to the GABAA-receptor complex in vitro. The inhibitory potencies of folates on [3H]muscimol and [3H]diazepam bindings did not correlate with their epileptogenic effects. However, folates reverse the inhibiting effect of GABA on the binding of the cage convulsant [3H]TBOB [( 3H]t-butylbicycloorthobenzoate). The rank order of this in vitro effect (folic acid greater than 5-HCO-H4 folate greater than H2 folate = 5-CH3-H4 folate) resembles the rank order of epileptogenicity determined in vivo. A relationship between the in vivo and in vitro effects is therefore suggested.

This document is available from: http://directlinks.cc/files/muscimol/2166659.pdf

Author List: Van Rijn C M, Van der Velden T J, Rodrigues de Miranda J F, Feenstra M G, Hiel J A, Hommes O R

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bridged-Ring Compounds; Convulsants; Formyltetrahydrofolates; Receptors, GABA-A; Tetrahydrofolates; Folic Acid; tert-butylbicyclo-2-benzoate;

Mesh terms: Animals; Brain/metabolism; Bridged Bicyclo Compounds/metabolism; Bridged Bicyclo Compounds, Heterocyclic; Bridged-Ring Compounds/metabolism; Convulsants/pharmacology; Epilepsy/chemically induced; Folic Acid/pharmacology; Formyltetrahydrofolates/pharmacology; In Vitro Techniques; Male; Rats; Rats, Inbred Strains; Receptors, GABA-A/metabolism; Tetrahydrofolates/pharmacology;

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