EFFECTS OF S-9977-2 ON HISTAMINE LEVELS IN RATS

S-9977-2 is a new molecule with promnesic and antiamnesic properties. In this study, we investigated the effects of i.p. administration of S -9977-2 on histamine (HA) levels in several regions of the rat brain, and also in peripheral areas, using high performance liquid chromatogr aphy (HPLC) with fluorometric detection. S-9977-2 (0.025 mg/kg) induce d an increase in the content of HA in the anterior hypothalamic region , with a significant effect 30 min after injection (1.77 +/- 0.36 nmol /g vs. 2.43 +/- 0.40 nmol/g; p <0.01). It did not significantly modify HA levels in the posterior hypothalamic region, hippocampus, fronto-p arietal cortex, blood spleen,or adrenal glands. A clear tendency to in crease HA content was observed in the hippocampus (0.16 +/- 0.03 nmol/ g vs. 0.39 +/- 0.31 nmol/g, ns) and fronto-parietal cortex (0.55 +/- 0 .45 nmol/g vs. 0.70 +/- 0.28 nmol/g; ns). S-9977-2 at doses of 0.005 a nd 0.125 mg/kg i.p. did not produce any significant change in HA level s in any of the samples tested 30 min after administration. The presen t results demonstrate that S-9977-2 increases HA levels in the anterio r hypothalamus, which is the brain region with the highest content in histaminergic fibers. This fact suggests that the neuronal HA system m ight be involved directly or indirectly in the pharmacological actions of S-9977-2.