Measuring side effects of drugs acting on the CNS

Usefulness of the methods

Some side effects, as e. g. changes in vigilance and performance, orthostatic dysregulation, respiratory depression, or anticholinergic and cholinergic effects, are typical for drugs or even drug groups acting on the CNS and should be investigated and quantified for labelling and regulatory purposes. With respect to these side effects new agents are often advantageous. Showing such a superiority may also be of great interest. HPR offers methods which fulfil these purposes.

The following methods which are frequently relevant for the measurement of side effects are presented in detail on extra pages:

• Measurement of vigilance and CNS performance
• Measurement in functional sleep disturbances
• Dynamometry, EMG.
• Tremor measurement.
• Measurement of drug-ethanol interactions

Hypercarbia for the investigation of respiratory depression

The subject inhales air which is step-wise enriched with up to 4 % CO2. The respiratory volume as the dependent variable, determines the respiratory response. The technique has successfully been used for measuring the effect of benzodiazepines, hypnotics and centrally acting analgesics on respiratory regulation.

Tilt table test

The tilt table test is used to determine the cardiovascular regulation to postural changes. Invasive and non-invasive haemodynamic parameters such as heart rate, systolic and diastolic arterial pressure, venous pressure, pulse wave transmission time as well as relative volume changes in the lower extremities (with venous occlusion plethysmography) are recorded and analysed on-line. With this test system we have documented impressive orthostatic dysregulations after the administration of antihypertensives and benzodiazepine-anxiolytics and hypnotics.

Dynamic and static IR-computer video pupillometry

In static pupillometry the pupillary disc area is determined at light and dark adaptation. In dynamic pupillometry one eye is stimulated by a sequence of weak light stimuli after reaching dark adaptation. The contra-lateral pupillary reflexes are measured. An infrared video camera takes images of the pupil and the pupillary area is electronically measured and evaluated with respect to latency, amplitude and the integral of the averaged response to light stimuli. With the IR-computer video pupillometry we have investigated anticholinergics, antidepressants, spasmolytics and cholinomimetic psychotropics.