Effect of JM-1232(-), a New Sedative on Central Respiratory Activity in Newborn Rats

Abstract

JM-1232(-), a newly manufactured isoindole derivative, shows sedative effect at a lower concentration compared with propofol. In the present study, we analyzed the response of the central respiratory activity to JM-1232(-). The brainstem-spinal cord of a newborn rat was isolated and was continuously superfused with oxygenated artificial cerebrospinal fluid (ACSF). Rhythmic inspiratory burst activity was recorded from C4 spinal ventral root using a glass suction electrode. We measured C4 burst rate and amplitude of integrated C4 activity. After obtaining a control recording, the preparation was superfused with ACSF containing JM-1232(-) at 10, 100 or 500 microM for 10 min. The application of both 10 and 100 microM JM-1232(-) did not decrease C4 burst rate significantly. However, 500 microM JM-1232(-) reduced C4 burst rate. On the contrary, C4 burst amplitude was not affected by the application of JM-1232(-) for 10 min at any concentrations. In conclusion, JM-1232(-) at a low concentration (but presumably higher than hypnotic dose), did not depress the central respiratory activity, whereas at a high concentration depression was seen.

The effects of topical and intravenous JM-1232(-) on cerebral pial microvessels of rabbits

“…Kuribayashi et al reported that JM-1232(-) at between 10 -4 and 5 x 10 -4 mol/L depressed central respiratory activity, and estimated that the hypnotic dose was less than 10 -5 mol/L [ 6 ]. As in rats, the effective concentration of JM-1232(-) in the rabbit is probably well under 10 -5 mol/L.…”