Comparison of local anesthetic activity of pentacaine (trapencaine) and some of its derivatives by three different techniques.
The local anesthetic potency of the carbanilic drug pentacaine (1; trapencaine) was compared to that of a series of its derivatives as well as procaine and cocaine. It is known that 1 exhibits potent local anesthetic, gastroprotective and antiulcer activities. The local anesthetic potency of the drugs under study was tested by three different techniques, i.e. analysis of compound action potential amplitude in rat sciatic nerve in vitro, duration of full anesthesia in rabbit cornea in vivo as well as in guinea-pig skin in vivo. The potency was expressed as drug concentration evoking either 50% reduction in action potential amplitude in the isolated nerve or anesthesia lasting for 20 min in the 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 comparatively good agreement was found in the orders of the drug potencies. Plotting local anesthetic potency and drug lipophilicity revealed a good positive correlation between these two parameters in the group of the drugs tested.
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Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
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D000200:Action Potentials / Q000187:drug effects; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002219:Carbamates / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003042:Cocaine / Q000494:pharmacology; D003315:Cornea / Q000187:drug effects; D004558:Electric Stimulation; D006168:Guinea Pigs; D007271:Injections, Intradermal; D011343:Procaine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000187:drug effects; D012879:Skin Physiological Phenomena
D000779:Anesthetics, Local; D002219:Carbamates; D011343:Procaine; C010618:pentacaine; D003042:Cocaine