VPT 321: Veterinary Neuropharmacology (2+1) copy 1

BARBITURATES - STRUCTURE ACTIVITY RELATIONSHIP

Barbiturates are derived from the nondepresssant barbituric acid which is a combination of malonic acid and urea.  Barbiturates are bitter tasting white powders. Salts containing sulfur have a yellowish tint. They are hygroscopic and will decompose on exposure to air, heat and light. 

Structure activity relationship

• To be hypnotically effective, both the hydrogen atoms on carbon5 must be replaced by an alkyl or arryl group.
• To obtain optimal therapeutic results, the substituting radicals on carbon 5 should contain a minimum of 4 and a maximum of 9 carbons. Addition of more carbon leads to convulsant activity.
• Unsaturated carbon chains are more readily oxidized and hence are short acting.
• Short chains are more stable and hence are long acting.
• Long chains are easily oxidized and are short acting.
• Branched chains tend to be shorter in action than straight chains.
• Only one aryl radical should be attached to carbon 5.
• Replacement of the oxygen atom on carbon 2 by a sulphur atom increases the potency and instability and shortens the duration of action of the compound. Barbiturates containing oxygen in carbon 2 are called oxybarbiturates and those containing sulphur are called thiobarbiturates.
• Attachment of an alkyl group to one of the N-atoms (position 1 or 3) increases the anaesthetic potency and tends to stimulate the CNS. Substitution in both the N-atoms produces a convulsant.
• Replacement of the oxygen on carbon 2 by an HN= group destroys the hypnotic activity of the molecule.

In USA ‘al’ is substituted in the name of barbiturates for ‘one’ (For example in USA thiopentone is known as thiopental). Barbituric acid and its carbon 5 derivatives are sparingly soluble in water. But, the sodium salts are, water soluble salts. Sodium salts of barbiturates are alkaline in nature and if injected perivascularly, there is tissue irritation. Inadvertent injection of barbiturates into smaller artery may lead to intense vasoconstriction, thrombosis and gangrene.