•In the lower dose range, excitement, increase activity, pregariousness, and
aggression may occur in some individuals.
•This phenomenon has commonly been attributed to the disruption of neural
pathways of higher cortical origin that play an inhibitory function of subcortical
centers of the brain= disinhibition.
BARBITURATES AND OTHER SEDATIVE—HYPNOTICS
•Barbiturates and other drugs in the sedative—hypnotic class have effects so similar
to alcohol’s effects, except to note that long-term alcohol exposure probably has more
toxic physiological consequences.
•Sedative-hypnotic compounds without the barbiturate structure, such as
methaqualone and glutethimide, have been synthesized, but their actions are
essentially indistinguishable from those of the barbiturates.
•Barbiturates differ from each other primarily in terms of pharmacokinetics, which
determines how quickly the drugs act, their intensity of action, and their duration of
action. (all three properties are tied together)
•These differences in these properties are a major factor in determining what these
drugs are used for. For example the ultrashort-duration ~15min is used as an
anaesthetic, they can be used as sedative, sleep inducers and an anticonvulsant.
•Over the past 3 years the medical use of these drugs has declined considerably,
primarily because of the development of newer compounds with less toxicity of
•They are no longer under patent, and thus they are very inexpensive.
•The general tendency of these drugs is to decrease the excitability of neurons
throughout the nervous system.
•Although barbiturates depolarize some neurons, their predominant action
throughout the nervous system is to hyperpolarize neurons.
•The inhibitory influence of barbiturates has been postulated to be due to their
ability to enhance GABA’s activity at the GABAA – type receptor, which results in the
opening of Cl- channels, allowing Cl- to slow into neurons and hyperpolarizing them.
•The primary action of barbiturates appears to be one of prolonging the duration that
these channels remain open.