The putative endogenous convulsant 3-hydroxykynurenine decreases benzodiazepine receptor binding affinity: implications to seizures associated with neonatal vitamin B-6 deficiency.

Abstract

The kynurenines, endogenous tryptophan metabolites with convulsant properties, have been postulated to play a role in the genesis of seizure disorders. We have previously reported that concentrations of 3-hydroxykynurenine (3-HK) higher than 0.2 mM are present in the brains of neonatal rats perinatally deprived of vitamin B-6. At a 1 mM concentration 3-HK significantly decreased the affinity of 3H-flunitrazepam for benzodiazepine receptor sites in rat brain membrane preparations. Furthermore, lower concentrations (Ki = 250 microM) of 3-HK antagonized the enhancing effect of GABA on 3H-flunitrazepam binding. These results suggest that 3-HK may have a modulatory effect on the GABA/benzodiazepine/barbiturate receptor complex.

• Authors: T R Guilarte, L D Block, H N Wagner Jr
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 30 Issue 3 Pg. 665-8 (Jul 1988) ISSN: 0091-3057 [Print] United States
• PMID: 2850579 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Convulsants
• Receptors, GABA-A
• 3-hydroxykynurenine
• Kynurenine
• gamma-Aminobutyric Acid
• Flunitrazepam

Topics

• Animals
• Brain (metabolism)
• Convulsants (pharmacology)
• Flunitrazepam (metabolism)
• Kinetics
• Kynurenine (analogs & derivatives, pharmacology)
• Male
• Rats
• Receptors, GABA-A (drug effects, metabolism)
• Seizures (physiopathology)
• Vitamin B 6 Deficiency (physiopathology)
• gamma-Aminobutyric Acid (metabolism)