Phase I Reactions: Reductive Reactions

Reductive reactions introduce electrons to drug molecules, affecting polar functional groups like hydroxy and amino, allowing subsequent biotransformation or conjugation.

Carbonyl group reductions transform aliphatic carbonyl compounds and aromatic and alicyclic ketones to alcohols. For example, naltrexone transforms into its isomorphine derivative.

C=C reductions, as seen in steroids like norethindrone, convert double bonds into single bonds. Alcohols undergo dehydration to alkenes before reduction, as exemplified by the metabolites of the antispasmodic drug bencyclane.

N-compound reductions transform nitro, azo, and N-oxide groups to their reduced forms. For instance, nitro reduction in nitrazepam proceeds via nitroso and hydroxylamine intermediates to yield an amine.

Prontosil, an azo drug, undergoes reduction to active sulfanilamide, while imipramine N-oxide is converted to imipramine.

Miscellaneous reductive reactions encompass various reduction processes in drug metabolism.

The anesthetic halothane undergoes reductive dehalogenation, and is converted to trifluoroacetic acid or its derivatives.