The kynurenate analog SZR-72 prevents the nitroglycerol-induced increase of c-fos immunoreactivity in the rat caudal trigeminal nucleus: comparative studies of the effects of SZR-72 and kynurenic acid.
Administration of nitroglycerol in a migraine model results in an increased number of c-fos-expressing secondary sensory neurons in the caudal trigeminal nucleus. Since synapses between first- and second-order trigeminal neurons are mediated by excitatory amino acids, NMDA receptors are inhibited by kynurenic acid, though this crosses the blood-brain barrier only poorly. Systemic treatment of rats with SZR-72, a newly synthetized kynurenic acid analog, diminished the nitroglycerol-induced increase of c-fos immunoreactivity in the brain stem highly significantly, while treatment with kynurenic acid resulted in a significantly smaller decrease, proving that SZR-72 is much more effective than kynurenic acid.
Knyihar-Csillik
E
E
Department of Neurology, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, 6 Semmelweis utca, H-6726 Szeged, Hungary. knyihar@nepsy.szote.u-szeged.hu
Mihaly
A
A
Krisztin-Peva
B
B
Robotka
H
H
Szatmari
I
I
Fulop
F
F
Toldi
J
J
Csillik
B
B
Vecsei
L
L
D000818:Animals; D002452:Cell Count; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014275:Trigeminal Caudal Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; C533052:SZR 72; D005996:Nitroglycerin; D007736:Kynurenic Acid