The respiratory rhythm is generated in a neural network in the "pre-Boetzinger-complex" which is located in the medulla oblongata. The rhythm is modified by many parameters (e.g. pCO2, pO2 and pH). Due to the enormous meaning of efficient respiration for living organisms we analyzed the influence of some common drugs (Verapamil, Prazosin, Sevofluran and 18-b- glycyrrhetinicacid) on respiratory activity using the in-situ- perfused-brainstem to record phrenic nerve discharges (as an indicator for changes of central respiratory activity).18-b-glycyrrhetinicacid decreased phrenic nerve discharge frequency at lower concentrations (0.1mM) down to 55±23.15% (p=0.012) of control. Concentrations of Prazosin at 20mM caused an increase of frequency up to 174±57.24% (p=0.156) of control. In 66% of the experiments a transient decrease of respiratory frequency (from 7±1.5 per minute to 4.2±1.2 per minute; ~40% increase) (over 10 to 30 min) was observed, followed by a clear increase (more than 50%). Control to minimum: p<0.001; control to maximum: p<0.03). Sevofluran concentration dependently increased the frequency of phrenic nerve discharges with a threshold concentration of 1nM (38±15%). At a concentration of 100nM the frequency was 75±12% above control value.

Although all experiments show a clear effect of applied pharmaceuticals on respiratory activity and rhythm; we were not able to answer by which mechanism the changes caused.