Analysis of site of action of zopiclone on the central respiratory and cardiovascular control mechanisms.

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Experiments were performed in vagotomized and paralyzed rabbits with severed carotid sinus nerves and maintained by artificial ventilation under monitoring O2 and CO2 levels in expired air. The phrenic nerve, renal sympathetic nerve activity and EEG were recorded simultaneously with arterial blood pressure and ECG. Effects of zopiclone were compared before and after brain stem transection at the mid-pontine level. Although the period of respiratory burst activity in the phrenic nerve was prolonged (before, 1.7±0.5 sec; after, 21.4±13.7 sec) after mid-pontine transection, the respiratory rhythmic activity was preserved with a slightly change in CO2 levels in expired air (before, 3.55±0.40%; after, 3.35±0.30%). After mid-pontine transection zopiclone (1-10 mg/kg i.v.) prolonged the period of the phrenic respiratory volley (28.3±13.0 sec, p<0.05, N =10) and reduced the total power of both the phrenic (27.8% of the control) and the renal nerve activities (41.0%) significantly. Zopiclone caused a significant decrease in mean blood pressure (27.2% of the control) and heart rate (2.6%). Furthermore the inhibitory action of zopiclone on CO2 response as measured by the total power of the phrenic nerve activity was also observed after the transection. The direction of these changes induced by zopiclone aftei mid-pontine transection was qualitatively the same as that before (Jpn. J. Pharmacol., 32(Suppl.), 66p). These results indicate that zopiclone exerts the respiratory and cardiovascular inhibitory action by acting on the part of the central respiratory and cardiovascular control mechanisms located caudal to mid-pontine level.