Procaine HCl, introduced in 1904 by Alfred Einhorn, was the first synthetic injectable local anesthetic. Its chemical structure, 2-Diethylaminoethyl 4-aminobenzoate hydrochloride, and rapid metabolism by plasma pseudocholinesterase distinguish it from the amides. This ester is quickly hydrolyzed in the plasma, producing para-aminobenzoic acid (PABA) and diethylaminoethanol. Less than 2% of the drug is excreted unchanged in the urine. Due to this rapid metabolism, procaine exhibits a very short half-life of 0.1 hours (6 minutes), limiting its duration of action and requiring frequent re-administration for prolonged procedures.
Procaine has a pKa of 9.1, resulting in a slow onset of action (6 to 10 minutes). Its pH in a plain solution is 5.0 to 6.5, and in vasoconstrictor-containing solutions, the pH ranges from 3.5 to 5.5. Despite these properties, procaine's potency is relatively low (1 on the potency scale), and it produces significant vasodilation, which complicates its use in surgeries requiring a bloodless field. Due to this vasodilation, procaine is also useful in emergency settings, such as in managing arteriospasm following inadvertent intra-arterial drug injection.
Although procaine was a pioneering anesthetic, it fell out of favor with the introduction of lidocaine in the mid-1940s. In dental practice, a 2% procaine solution provided only 15 to 30 minutes of soft tissue anesthesia and essentially no pulpal anesthesia without a vasoconstrictor. Because of its profound vasodilatory effects, it was difficult to maintain a clean surgical field. By the mid-1990s, procaine was largely removed from the market in North America, although its trade name, Novocain, remains synonymous with local anesthesia in common parlance. Notably, procaine still finds occasional use in special medical circumstances where amide anesthetics are contraindicated.
