Miloš Tijanić

HISTORICAL DEVELOPMENT OF LOCAL ANESTHETICS
USED IN STOMATOLOGY

Introduction

Nowadays, local anesthetics certainly present the medications most used in stomatology. At stomatological surgeries around the world, more than million ampoules of local anesthetics are being applied (only in SAD, stomatologists annually use more than 300 million of ampoules).¹ A contemporary stomatology, primarily oral surgery, cannot be imagined without the application of local anesthesia, and it certainly owes its advances to the discovery and constant improvement of local anesthetics. The history of the development of local anesthetics is in accordance with the history of the people's struggle against the pain. The availability of the safe, reliable and effective local anesthetics has significantly contributed to the reputation of the profession and enabled the development of many surgical procedures. This year 120 year anniversary has been celebrated since the first application of local anesthetic in stomatology. It is interesting to mention that the pioneers in the application of narcotics were ancient dentists, and that the first operation carried out in 1846 presented a tumor removal from the lower jaw.²
How was it discovered? How have local anesthetics been developing, starting from cocaine up to the present age?


The Discovery of Cocaine

The natives of South America were familiar with hallucinating effect of Erythroxylon coca thousands of years B.C. Moreover, its breading in the region of the Andes dates some 700 years B.C.³ The discovery and the conquest of South America made coca wellknown in European civilization. What is more, in the first part as well as in the middle of the sixteen century, coca was one of the subjects of conquistadors' correspondence. Spanish conquers noticed the natives heroically enduring hunger, physical effort and slave work. In addition, they noticed the natives occasionally chewing the leaves of a plant, up to then, unknown to Europeans. In 1574, the best-known Spanish physician of that time, Nicolas Bautista Alfaro published a text describing the form, use and the effects of coca.³

The first written document mentioning the anesthetic effect of coca originates from 1653. It was written by Bernardo Cobo, a Spanish Jesuit, who emphasized that toothache may be alleviated by chewing of coca leaves.3 Only two hundred years later, more precisely, in 1862, a chemist Albert Neiman (Göttingen, Germany), succeeded in isolating an active component he defined as cocaine.4 Only then did he notice that cocaine caused the numbness of tongue. The exact molecular formula (-C17H21N04-) was discovered by his disciple Wilhelm Lossen in 1865, whereas the structural formula was discovered by Richard Willstaeter in 1989.5 A Peru-vian military physician Moreno y Maiz, in his Ph. D. final, published in Paris in 1868, describing the effect of cocaine on experimental animals, pointed out in one footnote a significance of local anesthetic effect of cocaine. A researcher, Basil Von Anrep from the Uni-versity in Würzburg, in his paper published in1880, concluded that cocaine could be used in surgery as an anesthetic.⁶ In July, 1884, Sigmund Fraud published a monograph dedicated to cocaine.⁴ Even if many researchers were quite aware of the anesthetic effect of cocaine, there were no papers describing its application on the patients as a part of surgical action. That advance, very significant for medical sciences, happened in 1884 when a younger ophthalmologist Carl Koller from the general hospital in Vienna (Wiener Allgemeines Krankenhaus), after the experiment on animals, carried out for the first time on 11. September, applied the solution of cocaine as a local anesthetic, performing the operation on the eye in patient with glaucoma.⁴

It didn't pass long since the first application of cocaine in stomatology. Only a few months later, dr. Richard J. Hall and his associate dr. William Stewart Halster in New York's Medical Journal from 6. December, 1884, published his first experiences with the use of cocaine in stomatology.4 Namely, on 26. November, dr. Hall persuaded his stomatologist, dr. Nash, to apply the solution of cocaine (0,5ml 4% cocaine-hydrochloride) immediately before the filling of the first upper left incisive. The solution was applied submucosally, in the immediate vicinity of infra-orbital foramen. Two minutes after that, a full anesthesia was succeeded in the area of left half of the upper lip and cheek, which lasted for the next 26 minutes. On 1. December 1884, dr. Halsted carried out the first block anesthesia for n. alveolaris inferior applying the solution of cocaine to a student of medicine.⁴

After publishing of Coller's discovery, very quickly cocaine started to be wildly applied, primarily in stomatology. Soon, a drastic mani-festation of its side-effects (toxicity, addiction) started to occur due to its application in extremely high concentrations, even up to 30%. During the period between 1884 and 1891, 200 cases of extreme intoxication were recorded as well as 13 lethal outcomes after the application of cocaine.³ A great number of patients, including the pioneers in the examination of cocaine, S. Fraud and W. Hallsted, became addicts.


The development of synthetic local anesthetics

Due to the above mentioned a further research for local anesthetic which would replace cocaine was continued. A significant progress was made by a German chemist Alfred Einhorn, who synthesized Novocain (ester of paraaminobensal accid), at the end of 1904.⁷ Having been remained into procaine later, this anesthetic started to be widely used primarily due to its safer application in relation to its precursor and despite its shortcomings as well. The main disadvantages of procaine are above all short-lasting effect (to prevent it, vasoconstrictor in larger concentration was added), and usual occurrence of allergic reactions, which is the reason why its use in stomatology was abandoned. The most potent of all local anesthetics of Estar type, tetracaine, was synthesized in 1930, yet, it is not used as well in stomatology today (except for the surface anesthesia).⁸

A great progress was made in 1943 by synthesing the first local anesthetic of amid group. Its founders Nils Löfgren and Bengt Lundquist called it lidocaine.⁷ Even today, lidocaine is the local anesthetic most frequently in use in stomatological praxis, thanks to its safety in use, a satisfied anesthetic effect, as well as the fact that it very rarely causes allergies in patients.

In the second half of the last century, a further development of local anesthetics belonging to amid type, judging by its structure, was continued. In 1957, Ekenstam synthesized mepivacaine and bupivacaine, a longacting effect anesthetics which were used most.⁹ Nils Löfgren and Claes Tegner synthesized prilocaine in 1976. In the same year, Rusching synthesized articaine¹⁰, and in 1972 Adams and associates did the same with etidocaine.¹¹

Perceiving the fact that bupivacaine and etidocaine in relation to the available local anesthetics of short-acting effect have dispro-portionally larger potential for causing either CNS or CVS fluids¹², the formation of long-effect local anesthetics started so as to eliminate the present of the above mentioned side effects. Further researches enabled the introduction of ropivacaine into surgical praxis in 1996.¹³ Ropivacaine is a local, long-lasting anesthetic, very similar to bupivacaine as far as its chemical and anesthetic effect is concerned; however, it is far less cardiotoxic than bupivacaine.¹⁴ Ropivacaine has one feature that differentiates it from other local anesthetics and that is vasoconstrictor effect on the very spot of its application.¹³ The remainder local anesthetics with the exception of cocaine, cause vasodilatation, so they are mostly used with the addition of vasoconstrictor in local anesthetic solution. Very few data concerning the application of ropivacaine in stomatology are available today. In 2003, ropivacaine was successfully used as local anesthetic in oral surgery.¹⁵ Very close to be introduced in a wide surgical praxis is levobupivacaine as well (S-ent anomer of bupivacaine), which is also claimed to be less toxic in comparison to bupivacaine.¹⁶

Even if a long way has been passed in the development of local anesthetics since their first application, more than a century ago, up to the present age, contemporary medicine and stomatology still don't have an ideal local anesthetic at hand. Therefore, the intensive researches directed towards the achievement of that goal are being continued even today.


References

1. Haas D. An update on local anesthetics in dentistry. J Can Dent Assoc 2002;68(9): 546-551.

2. Matou{ek M. Materialy k dejinam stomatologie. Praha, SPN; 1963.

3. Calatayud J, Gonzalez A. History of the develo-pment and evolution of local anesthesia since the coca leaf. Anesthesiology 2003; 98(6):1503-1508.

4. Leonard M, Carl Koller. Mankind's greatest benefactor? The story of local anesthesia. J Dent Res 1998; 77(4): 535-538.

5. Dullenkopf A, Borgeat A. Lokalanaesthetika- Unterschiede und Gemeinsamkeiten der "-caine". Anaesthesist 2003; 52:329-340.

6. Biscoping J, Bachmann-Mennenga M. Lokal anaesthetika vom ester zum isomer. Anaesthesiol Intensivmed Notfallmed Schmerzther 2000;35:285-292.

7. Gotta A, Donovan R, Sullivan C. The pharmacology of local anesthetics. Ophtalmology Clinics of North America 1998;11(1): 11-23.

8. Cox B, Durieux ME, Marcus M. Toxicity of local anesthetics. Best Practice & Research Clinical Anesthesiology 2003;17(1):111-136.

9. Laskin J, Wallace W, DeLeo B. Use of bupivacaine hydrochloride in oral surgery-a clinical study. J Oral Surg 1977;35:25-29.

10. Malamed S, Gagnon S, Leblanc D. Efficacy of articaine: a new amide local anesthetic. JADA 2000; 131:635-642.

11. Laskin J. Use of etidocaine hydrochloride in oral surgery:a clinical study. J Oral Surg 1978;36:863-865.

12. Mather L, Chang D. Cardiotoxicity with modern local anesthetics.Drugs 2001;61(3):333-342.

13. McClellan K, Faulds D. Ropivacainean update of its use in regional anesthesia. Drugs 2000; 60(5):1065-1093.

14. Graf B, Abraham I, Eberbach N, Kunst G, Stowe D, Martin E. Differences in cardiotoxicity of bupivacaine and ropivacaine are the result of physicochemical and stereoselective properties. Anesthesiology 2002; 96(6): 1427-1434.

15. Burić N: Ropivacaine as local anesthetic in the surgery of maxillary sinus. Acta Stomatologica Naissi, 2003; 19 (44): 167-172.

16. Fawcett J, Kennedy J, Kumara G, Zacharias M. Comparative efficacy and pharmacokinetics of racemic bupivacaine and S-bupivacaine in third molar surgery. J Pharm Pharmaceut Sci 2002;5(2):199-204.
     

Adress for correspondence:

Miloš Tijanić, D.D.S.
Clinic of Stomatology - Niš
52 Braće Tasković Street
18000 Niš, Serbia and Montenegro
E-mail: tijanicm@yahoo.com

• Copyright © 2003 by The Editorial Council of The Acta Stomatologica Naissi