PROCAINE

(Novocain)

What is Procaine?

It is the first injectable local anesthetic to be synthesized, commonly known as Novocain.The German Chemist, Alfred Einhorn, developed it in 1904.

What company originally developed Procaine?

In 1911, Dr. Mendal Nevin founded Novocol Chemical Manufacturing Company, Inc. The Company imported Procaine into the United States from Germany.The U.S. Government granted the first license to synthesize and manufacture Procaine when the United States entered World War I.With license in hand, Dr. Nevin set his private dental practice aside and devoted his full time to manufacturing Procaine in the United States.Novocol is currently owned by Deproco Incorporated.

How does Procaine work?

Procaine temporarily prevents the sense organs from initiating afferent impulses and provides regional analgesia.

It works by producing a trigeminal nerve conduction block, in the mandibular (3rd) branch, decreasing the permeability of the axon cell membrane to (Na+) sodium ions.This mechanism prevents the entry of Na+ ions into the axon to propagate an action potential in both slow and fast pain fibers.Unmyelinated axons are the first to be affected.Myelinated motor nerves are only affected at the nodes of Ranvier.Procaine works to anesthetize a patient for about 15 minutes.To prolong anesthesia epinephrine is added as a vasoconstrictor.

What plant was procaine derived from?

The coca plant.It is a member of the order Geraniales and the family Erythroxylaceae.Bolivian coca grows in the moist tropical forests of the eastern Andes of Peru and Bolivia. This variety is one of four found growing in the wild. Bolivian coca is the major source of commercially produced coca leaves and cocaine.Procaine is the precursor to cocaine.

Novocaine means “new cocaine.”

Cocaine versus Procaine...

Cocaine blocks Na+ passage through the axon cell membrane and inhibits the reuptake of Dopamine and Serotonin resulting in psycho-stimulation.Procaine blocks nerve conductance via inhibiting Na+ at the membrane, thus no psycho-stimulation.Both reactions are brief.

Side effects? 

Despite the past widespread use of procaine, reports of side effects have been rare, and are usually associated with excessive dosage, rapid absorption or inadvertent intravascular injection. Lightheadedness, irregular heart beats and allergic reactions have rarely been reported for oral procaine.Very rarely an allergic reaction may cause seizure.

There are two types of local anesthetic drugs: ester and amide.Procaine is an ester-type.Allergic reactions that occur are usually not in response to Procaine, but rather to para-aminobenzoic acid (PABA) which is a major metabolic product of all ester-type local anesthetics.Procaine is metabolized in the plasma by the enzyme pseudocholinesterase, an enzyme involved in the breakdown of acetylcholine, it is similar to acetylcholinesterase.However acetylcholinesterase is found in the nerve tissue and pseudocholinesterase is found primarily in the liver.Procaine undergoes hydrolysis (the splitting of a compound into fragments by the addition of water, the hydroxyl group being incorporated in one fragment and the hydrogen atom in the other) and breaks into para-aminobenzoic acid (PABA), which is excreted unchanged in the urine, and diethylamino alcohol, which undergoes further transformation prior to excretion.The structure of PABA is common to many other antigenic compounds and is thought to account for allergic reactions. 

Approximately 1 in 3000 persons has an atypical form of pseudocholin-esterase, resulting in the inability to hydrolyze procaine and other ester-type local anesthetics. This in turn causes a prolongation of high blood levels of the procaine and increased toxicity. 

Who should not take this medication? 

People who have experienced allergy to the drug should not take it.Fortunately, true allergic reaction to procaine is rare. However, adverse reactions (anesthetic overdose, fainting) appear to be common.Differentiating between allergic reactions and resistance to the drug is often difficult because of the similarity of the symptoms.Thus, many physicians are conservative and label patients as "allergic" to all "caine" drugs even when the signs and symptoms are consistent with an adverse reaction.Unfortunately, this conservative decision often results in the patient being denied the comfort of a local anesthetic when desirable.

Drug Interactions?

Procaine is thought to reduce the effects of sulfonamide antibiotics.

How is this medication administered?

Oral injection.

Cost?

Procaine is very cost effective for short term local anesthesia.The patient only pays for regional anesthesia opposed to full-body anesthesia.It is $77 per 100 grams and only 40mg is necessaryfor the minimum dosage.However, procaine is used infrequently.It’s brief affects are no competition for the newer, longer lasting, local anesthetics available today.

Sources

1. Adverse Drug Interactions in Dental Practicehttp://www.db.uth.tmc.edu/faculty/vlewis/Vahnspage/2561/Drug_Interactions.htm#locals

2. Allergy to Local Anesthetics

"http://www.theberries.ns.ca/Archives/anaesthetics.html" 

3. Brief History of Products and Services

http://www.septodont.ca/Novocol/english/main/History.htm

4. Clinical Trial Update

http://www.aegis.com/news/bw/1999/BW990715.html

5.Current Medicinal Chemistry

Central Nervous System Agents

http://www.bentham.org/cmccnsa/index2.htm 

6. Everything2http://www.everything2.com/index.pl 

7.History of Dentistry

http://cudental.creighton.edu/htm/history.htm

8. Journal of Bangladesh Orthopedic Society

http://www.bdorth.org/Journal005.html 

9."Local Anesthetics"http://nnd40.med.navy.mil/Gen_Dent/Gen_Dent/Pearlsd6.HTMClassificatio

10. Ray, Oakley: Drugs, Society, and Human Behavior, Boston, 1999.

11. The Physiology of Analgesia

http://www.staffs.ac.uk/schools/sciences/psychology/coursematerials/pain/pptfiles/Physiology%20of%20Analgesia.ppt

12. The Pharmaceutical Industry 1905-52

http://www.aphanet.org/about/sesquisept01.html 

13. Tortora, Gerard: Introduction to the Human Body 5th Edition, New York, 2001.

14.Vasoconstrictors added to local anesthetic solutions

http://www.pharmacology2000.com/Central/Local_Anes/LAobj1.htm#Vasocontrictors%20added%20to%20local%20anesthetic%20solutions

15. Weil, Andrew: From Chocolate to Morphine, New York, 1998.

Compiled by: Mee-Na Walker

February 2003