Central Nervous System Depressants - Sedative - Hypnotic
Hypnotic and sedative drugs are non-selective, general depressants
of the central nervous system. If the dose is relatively low,
a sedative action results in a reduction in restlessness and
emotional tension. A larger dose of the same drug produces a
hypnotic sleep inducing effect. As the dosage is increased further,
the result is anesthesia or death if the dosage is sufficiently
The barbiturates once enjoyed a long period of extensive use
as sedative-hypnotic drugs; however, except for a few specialized
uses, they have been largely replaced by the much safer benzodiazepines.
Barbiturates are CNS depressants and are similar, in many
ways, to the depressant effects of alcohol. To date, there are
about 2,500 derivatives of barbituric acid of which only 15 are
used medically. The first barbiturate was synthesized from barbituric
acid in 1864. The original use of barbiturates was to replace
drugs such as opiates, bromides, and alcohol to induce sleep.
The hyponotic and sedative effects produced by barbiturates
are usually ascribed to their interference of nerve transmission
to the cortex. Various theories for the action of barbiturates
include: changes in ion movements across the cell membrane; interactions
with cholinergic and non cholinergic receptor sites; impairment
of biochemical reactions which provide energy; and depression
of selected areas of the brain.
The structures of the barbiturates can be related to the duration
of effective action. Although over 2000 derivatives of barbituric
acid have been synthesized only about a dozen are currently used.
All of the barbiturates are related to the structure of barbituric
acid shown below.
The duration of effect depends mainly on the alkyl groups
attached to carbon # 5 which confer lipid solubility to the drug.
The duration of effective action decreases as the total number
of carbons at C # 5 increases. To be more specific, a long effect
is achieved by a short chain and/or phenyl group. A short duration
effect occurs when there are the most carbons and branches in
the alkyl chains.