Subject(s)
Anti-Anxiety Agents/pharmacology , Adrenal Cortex Hormones/metabolism , Amino Acids/metabolism , Animals , Anti-Anxiety Agents/history , Anxiety/physiopathology , Behavior, Animal/drug effects , Benzodiazepines , Brain Chemistry/drug effects , Cerebellum/drug effects , Ganglia/drug effects , Humans , Ions/metabolism , Learning/drug effects , Memory/drug effects , Neurotransmitter Agents/metabolism , Neurotransmitter Agents/physiology , Psychopharmacology , Social Behavior , Spinal Cord/drug effectsABSTRACT
Sedative drugs are intended to cause various degrees of drowsiness. Animal experiments indicate that barbiturates induce these effects primarily by depression of the reticular activating system in the rostral brainstem. This in turn potentiates the thalamic recruiting system, thereby inducing 'barbiturate bursts' in the EEG. Anxiolytic drugs are intended to reduce anxiety or tension at doses which do not cause sedation or sleep. Propanediols may depress deactivating centers in the caudal brainstem, thereby releasing the activating centers in the rostral brainstem and depressing the thalamic recruiting response. These drugs may also act on the amygdala. Benzodiazepines have depressant effects on the amydala or hippocampus. These effects may release the reticular formation from inhibition. Enhanced activity of the activating and deactivating centers, to a different extent in different animals, would produce restlessness in some animals and sedation in others, accompanied by a mixture of fast and slow waves in the EEG. Sedative and anxiolytic agents also have central relaxant effects. The barbiturates act directly on the spinal cord, depressing both monosynaptic and polysynaptic reflexes. Propanediols and benzodiazepines act primarily on the descending facilitatory influence of the brainstem. Reduction of this influence depresses spinal polysynaptic but not monosynaptic reflexes. Biochemical studies suggest that barbiturates may act by antagonizing synaptic excitation induced by glutamate. Benzodiazepines may act by enhancing presynaptic inhibition mediated by GABA. The mechanism of action of propanediols is unknown.
Subject(s)
Anti-Anxiety Agents/pharmacology , Central Nervous System/drug effects , Hypnotics and Sedatives/pharmacology , Animals , Barbiturates/pharmacology , Benzodiazepines/pharmacology , Brain/drug effects , Brain Stem/drug effects , Drug Evaluation, Preclinical , Electroencephalography , GABA Antagonists , Medulla Oblongata/drug effects , Neural Inhibition/drug effects , Propylene Glycols/pharmacology , Reflex, Monosynaptic/drug effects , Spinal Cord/drug effects , Synapses/drug effectsABSTRACT
The effects of pentobarbital and diazepam were compared in a series of tests in squirrel monkeys; the effects of phenobarbital and flurazepam were compared in a second series. Observations were made of gross behavior and on the ECoG; the latter was analyzed by the spectral density technique. The two barbiturates induced sedation,which was occasionally so deep that the monkeys could not be readily aroused. The benzodiazepines induced sedation in some monkeys, but others showed signs of restlessness. The ECoG showed general slowing with the barbiturates, whereas the benzodiazepines produced mixed fast and slow patterns. Spectral density analysis showed that pentobarbital increased activity at frequencies below 40 Hz, with the largest increases occurring below 8 Hz. Phenobarbital increased activity below 8 Hz, but differed from pentobarbital by decreasing activity above 13 Hz. The benzodiazepines increased activity below 8 Hz, decreased it between 8 and 20 Hz, and increased it between 20 and 50 Hz.
