Barbital Interaction Test

A further consideration is which barbiturate to employ. We recommend the use of barbital because this substance, in contrast to many other barbiturates, undergoes no metabolism (Remmer 1972 Simon et al. 1992). For this reason, results obtained can be more readily interpreted in terms of a pharmacological interaction without confounding by pharmacokinetic or metabolic factors. 

Chapter I.C Central Nervous System (CNS) Safety Pharmacology Studies 

placed in individual macrolon cages (25 x 19 x 13 cm), are injected with barbital sodium (150 mg/kg i.p.). The latency to sleep and the duration of sleep (maximum 6 hours after barbital injection) are then recorded. Sleep is indicated by loss of the righting reflex. To avoid disturbing the experiment, no righting reflex test is performed before 50 minutes has elapsed after barbital injection (i.e. minimum sleep latency = 50 minutes). 

Ten rats are studied per group. The test is performed blind. 

The test substance is usually evaluated at 4 doses, administered p.o. 60 minutes before barbital, and compared with a vehicle control group. 

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The present Section describes basic protocols satisfying ICH S7A recommendations for core battery CNS studies. Included are protocols for measuring general behavioral signs induced by test substances (Irwin Test), effects on spontaneous locomotion (Activity Meter Test), effects on neuromuscular coordination (Rotarod Test), effects on the convulsive threshold (Electroconvulsive Shock (ECS) Threshold and PTZ Seizure Tests), interaction with hypnotics (Barbital Interaction Test) and effects on the pain threshold (Hot Plate Test). 

Fig. 5. Sleep/wakefulness in the Rat Barbital Interaction Test. Effects of caffeine and diazepam (p.o.) on the duration of sleep induced by barbital in the rat.

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