Local anesthetics from ester to isomer
by
Biscoping J, Bachmann-Mennenga MB.
Klinik fur Anaesthesie und Operative Intensivmedizin,
St. Vincentius-Krankenhauser, Karlsruhe.
Anasthesiol Intensivmed Notfallmed Schmerzther 2000 May;35(5):285-292


ABSTRACT

The use of chemical substances to prevent or treat local pain had its origin in South America. It was known that central nervous system stimulation occurred among the natives of Peru who chewed the leaves of an indigenous plant (Erythroxylon coca). Circumoral numbness was believed to have occurred as a by-product of this custom. Attempts to isolate the active principle from these leaves finally resulted in the isolation of the alkaloid, cocaine, by Niemann in 1860. The clinical usefulness of cocaine was not appreciated until 1884, when Koller reported upon topical anesthesia of the eye. The chemical identification of cocaine as a benzoic acid ester led to the synthesis of numerous compounds which were basically benzoic ester derivates. In 1905, Einhorn reported the synthesis of procaine. Tetracaine, the most potent ester of the benzoic acid series appeared in 1930. A major breakthrough in the chemistry of local anesthetic agents occurred in 1943 when Loefgren synthesized lidocaine, since it was not an ester but an amide derivate of diethylamino acetic acid. Concerning structure-activity relationships, local anesthetic agents, in general, possess the chemical arrangement of: aromatic portion--intermediate chain--amine portion. Changes in the aromatic or amine portion of a local anesthetic substance will alter its lipid/water distribution coefficient and its protein-binding characteristics which, in turn, will markedly alter the anesthetic profile. The toxic effects of long-acting local anesthetics on brain and heart, firstly reported by Albright, provided the initial stimulus to develop new amide-type local anesthetics. The first of these drugs, which has come into clinical practice was ropivacaine, the S-enantiomer of two possible optical isomers. It is structurally related to bupivacaine and mepivacaine, exerting a different pharmacodynamic profile, specifically on cardiac electrophysiology (less arrhythmogenic than bupivacaine). Studies on the anesthetic activities and toxicity of the individual enantiomers of bupivacaine and mepivacaine generally indicate, that the S-enantiomers are longer-acting and less toxic than the R-enantiomers.


TAC
History
Acupuncture
Crack and crime
Dopaminergic flies?
Dopaminergic agents
Freebasing flies go hyperkinetic
Local anaesthesia: from cocaine to ropivacaine


01 02 03 04 05 06 07 08 09 10 11 12
13 14 15 16 17 18 19 20 21 22 23 24


Refs
HOME
HedWeb
Cannabis.net
Future Opioids
BLTC Research
Wirehead Hedonism
Paradise-Engineering
Utopian Pharmacology
The Hedonistic Imperative
Anaesthetics and Anaesthesia
When Is It Best to Take Crack Cocaine?

swan image
The Good Drug Guide
The Responsible Parent's Guide To
Healthy Mood Boosters For All The Family