Thioperamide, antagonist of histamine H3 receptors, increases brain production of kynurenic acid
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Department of Otolaryngology, The Cardinal Rev. Wyszyński’s Voivodship Specialistic Hospital, Lublin, Poland
Department of Surgery, Oncology Centre, Lublin, Poland
Department of Experimental and Clinical Pharmacology, Medical University, Lublin, Poland
Department of Toxicology, Institute of Agricultural Medicine, Lublin, Poland
Ewa Urbańska   

Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
J Pre Clin Clin Res. 2010;4(1):11–13
Brain histamine plays the role of neuromodulator and neurotransmitter in a variety of physiological and pathological processes. Kynurenic acid (KYNA) is an antagonist of the glycine site within the N-methyl-D-aspartate (NMDA) receptor complex, and of nicotinic α7 receptors in the brain of mammals. Here, we report that thioperamide, H3 receptor antagonist/inverse agonist is capable of increasing KYNA synthesis in vitro. The effective concentrations were within the range of 0.25-1.0 mM in rat brain cortical slices, and 50-100 μM in mixed glial cultures. An inhibitor of protein kinase A, KT 5720 (0.5 μM) prevented the stimulatory effect of 0.5 mM thioperamide. Thioperamide also increased the activity of KYNA biosynthetic enzyme, KAT I, but not of KAT II. The above data suggest that the neuroprotective action of thioperamide may, at least in part, depend on an enhanced synthesis of KYNA.
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