Page 127 - Chemical and process design handbook

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BARBITURATES

Barbiturates are sedative drugs that are derived from barbituric acid and
have the ability to depress the central nervous system and act especially
on the sleep center in the brain, thus their sedative and sometimes hyp-
notic effects.
The method of synthesis for thousands of barbital analogs involves the
reaction of urea with various derivatives of malonic acid, usually a diethyl
ester of a dialkyl-substituted malonic acid.
The barbiturates are usually administered as the sodium salts. The N-H
bonds are acidic and although barbituric acid itself is inactive, a range of
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activities is obtained that varies with the groups at R and R . Activity and
toxicity both increase with the size of the groups. Branching and unsatura-
tion decrease the duration of action.
Barbiturates have been used in sleeping pills, but in recent years several
other compounds also have been introduced for this purpose. Barbiturates
induce a feeling of relaxation, usually followed by sleep, and have been used
to provide temporary respite in times of unusual emotional stress, but they
will only prolong the stress and patient reliance on the drugs is common.
The maximum therapeutic index (tolerated dose/minimum effective
dose) is highest when the two groups have a total of 6 to 10 carbons. Major
drawbacks of their use are their habit formation and their high toxicity
when alcohol is present in the bloodstream.

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