INTRODUCTION

In all those applications the final effect of the local anesthetics is an inhibition of electrical activity, accomplished as a reduction or total blockade of action potentials. The primary site of action is the sodium channel, transmembrane protein which is essential for the influx of sodium ions that subserves impulse generation and propagation in nerves, skeletal muscle and heart.  

Despite of the wide use of this type of compounds and the large amount of derivatives synthesized, only a few are currently used. Most of them belong to the family of lidocaine (amides) although some esters are also used. Their clinical efficacy and safety are rather satisfactory although sometimes some cardiac side effects and toxicity on CNS are seen. Sometimes, the duration of the anesthetic effects must be enhanced and this is accomplished by adding epinephrine to constrict capillaries in the site of the injection and to maintain high local concentrations of the drug. In general, local anesthetics are rapidly metabolized and cleared from the site of the injection.  

In order to improve the tissue distribution and fixation of the anesthetic molecule, scientists at IQB designed a series of amide anesthetic derivatives bearing a cyclopropyl group linked to the side chain (fig.1) This low molecular alkyl group maintains the steric and lipophylic properties of the most potent amide anesthetics such as bupivacaine but seems to be less sensitive to enzymatic metabolization thus maintained a higher duration of action.  

From this series, IQB-9302 was selected as a promising candidate to enter a pharmacological and clinical development.