R-zacopride, a 5-HT3 antagonist/5-HT4 agonist, reduces sleep apneas in rats.

The effects of R-zacopride, a benzamide with potent 5-HT3 receptor antagonist and 5-HT4 receptor agonist properties, on spontaneous apneas were studied in 10 Sprague-Dawley rats by monitoring respiration and sleep for 6 h. R-zacopride (0.5, 1.0 and 10.0 mg/kg) suppressed spontaneous central apneas during non-rapid-eye-movement (NREM) sleep by 50% (P=.05 for 0.5 mg/kg, P=.02 for 1.0 mg/kg and P=.001 for 10.0 mg/kg dose vs. control), and during rapid-eye-movement (REM) sleep by 80% by all doses tested (P<.0007) for at least 2 h after intraperitoneal injection. We conclude that R-zacopride, over a 20-fold dose range, significantly reduces central apnea expression during NREM and REM sleep in the rat. The efficacy of this compound to suppress central apneas most probably arises from its antagonist actions at 5-HT3 receptors or from its mixed agonist/antagonist profile at 5-HT4/5-HT3 receptors.