Effect of SX-3228, a selective ligand for the BZ1 receptor, on sleep and waking during the light-dark cycle in the rat

Abstract

The effects of the benzodiazepine 1 (BZ 1 ) receptor agonist SX-3228 were studied in rats (N = 12) implanted for chronic sleep procedures. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228, sc, to rats 1 h after the beginning of the light phase of the light-dark cycle induced a significant reduction of rapid-eye-movement sleep (REMS) during the third recording hour. Moreover, slow wave sleep (SWS) was increased during the fourth recording hour after the two largest doses of the compound. Administration of 0.5, 1.0 and 2.5 mg/kg SX-3228 one hour after the beginning of the dark period of the light-dark cycle caused a significant and maintained (6-h recording period) reduction of waking (W), whereas SWS and light sleep (LS) were increased. REMS values tended to increase during the entire recording period; however, the increase was statistically significant only for the 1.0 mg/ kg dose during the first recording hour. In addition, a significant and dose-related increase of power density in the delta and the theta regions was found during nonREM sleep (LS and SWS) in the dark period. Our results indicate that SX-3228 is a potent hypnotic when given to the rat during the dark period of the light-dark cycle. Moreover, the sleep induced by SX-3228 during the dark phase closely resembles the physiological sleep of the rat.

Effects of Compression and Grinding on Chemical Stability of a Benzodiazepine Receptor Agonist

“…[9][10][11][12][13] This compound is a non-benzodiazepine derivative with demonstrable selectivity for the benzodiazepine w 1 receptor subtype. [9][10][11][12][13] Although intended to be developed as a tablet preparation, the drug substance turned out to be chemically unstable in tablet form even though its stability was comparatively good in the powder mixture for tableting.…”

Stabilization Study on a Wet-Granule Tableting Method for a Compression-Sensitive Benzodiazepine Receptor Agonist

“…[3][4][5][6][7] This compound is a non-benzodiazepine derivative with demonstrable selectivity for the benzodiazepine w 1 receptor subtype. [3][4][5][6][7] Although intended to be developed as a tablet preparation, the drug substance turned out to be chemically unstable after compression. The authors announced in the previous report that this instability was due to decreasing crystallinity caused by compression.…”