Structure of Nitroglycerin
Nitroglycerin, also known as glyceryl trinitrate, is a nitrate ester of glycerol. It contains three nitrate groups esterified to the three hydroxyl groups of glycerol.
Chemical Formula: C₃H₅N₃O₉
Mode of Action
Nitric Oxide Release: Nitroglycerin is metabolized to release NO.
Vasodilation: NO activates guanylate cyclase, increasing cyclic GMP and causing smooth muscle relaxation.
Reduction of Cardiac Workload: Dilates veins more than arteries, reducing venous return (preload) and myocardial oxygen demand.
Uses
Angina Pectoris: Acute relief of anginal attacks.
Heart Failure: Management of acute decompensated heart failure.
Hypertension: As an adjunct in hypertensive emergencies.
Anal Fistulas: Applied topically to promote vasodilation and reduce pressure.
Structure-Activity Relationship (SAR)
Nitrate Ester Groups: Essential for NO release; the number and position of nitrate groups influence potency and duration.
Glycerol Backbone: Provides flexibility, allowing proper orientation for enzyme-mediated NO release.
Hydroxyl Substituents: Affect solubility and bioavailability.
Synthesis
Nitroglycerin is synthesized through the nitration of glycerol with a mixture of concentrated nitric acid and sulfuric acid.
Synthetic Route:
Starting Material: Glycerol (1,2,3-propanetriol).
Nitration Reaction: React glycerol with nitric acid in the presence of sulfuric acid as a catalyst.
Purification: Isolate nitroglycerin by neutralizing the reaction mixture and performing recrystallization.
Reaction Scheme:
CH₂OH-CHOH-CH₂OH + 3 HNO₃ → C₃H₅N₃O₉ + 3 H₂O