COMPARISON OF LOCAL-ANESTHETIC ACTIVITY OF PENTACAINE (TRAPENCAINE) AND SOME OF ITS DERIVATIVES BY 3 DIFFERENT TECHNIQUES

The local anesthetic potency of the carbanilic drug pentacaine (1; tra pencaine) was compared to that of a series of its derivatives as well as procaine and cocaine. It is known that 1 exhibits potent local anes thetic, gastroprotective and antiulcer activities. The local anestheti c potency of the drugs under study was tested by three different techn iques, i.e. analysis of compound action potential amplitude in rat sci atic nerve in vitro, duration of full anesthesia in rabbit cornea in v ivo as well as in guinea-pig skin in vivo. The potency was expressed a s drug concentration evoking either 50% reduction in action potential amplitude in the isolated nerve or anesthesia lasting for 20 min in th e other two techniques. The most powerful anesthetics were found to be 1, K1905, and K2002 with their potency exceeding that of procaine and cocaine by 1-2 orders. The derivatives P1, P2, and P3 were much less effective, their potency being comparable to the two reference drugs. Although there were remarkable differences in the ranges of effective concentrations of particular drugs in the techniques used, a comparati vely good agreement was found in the orders of the drug potencies. Plo tting local anesthetic potency and drug lipophilicity revealed a good positive correlation between these two parameters in the group of the drugs tested.