The Action of Local Anaesthetics on Experimental Epilepsy in Cats and Monkeys

Abstract

Very little attention has been paid to the action of local anaesthetics on the functions of the central nervous system. In the current literature there is no mention of their striking effect, which will be dealt with in this paper, on experimental epileptic attacks and related central phenomena. A thorough search of the literature revealed two papers by Mercier (1950a and b) on the effect of different local anaesthetic drugs on audiogenic seizures in albino rats given subconvulsive doses of various convulsants. As far as we know no attention has been paid to these investigations, which seem to be the first to indicate that local anaesthetics, such as procaine, have an anticonvulsant effect.We have studied the effects of different local anaesthetics on the electrically evoked epileptiform cortical after-discharge and related corticospinal phenomena, and compared them with the effects of these drugs on spinal functions and ascending transmission mechanisms. Preliminary reports on the central effects of lidocaine have already appeared (Bernhard and Bohm, 1954c and d). We have also compared the antiepileptic effect of these substances and barbiturates and of combinations of barbiturates and local anaesthetics. These investigations form the basis for the therapeutic use of a local anaesthetic, lidocaine (lignocaine A.N., " xylocaine "), for the rapid abolition of severe grand mal attacks and of post-operative epileptic seizures (Bernhard, Bohm, and Hdjeberg, 1955). METHODSCats and monkeys were used. Recordings of the epileptiform cortical after-discharge following repetitive cortical stimulation were made from the exposed brain. It is well known that the duration of the poststimulatory epileptiform cortical after-discharge depends on such stimulation characteristics as total duration, frequency, and strength (see, for example, Noel, 1941;Walker and Johnson, 1948; Bernhard, Bohm, and Taverner, 1954) McCulloch, 1937McCulloch, , 1939 Bernhard et al., 1954). The type of cortical after-discharge and of the accompanying motoneurone activity, which in the non-curarized state results in epileptiform muscular convulsions, also varies with these different factors. Based on our recent studies of experimental epilepsy (Bernhard et al., 1954), we used stimuli of about 1 msec. at 25/sec. for a total duration of 5 sec. The corticogram was recorded throughout the experiment, and cortical stimulation was not repeated until the corticographic changes from the preceding stimulation had disappeared. Usually there was a pause of 3-4 min. between each series of cortical stimulations. Pentobarbitone sodium, usually 15 mg./kg., was injected before the operation (opening of the skull, dissection of nerves, and sometimes laminectomy). Often 5 mg./kg. pentobarbitone was given after operation and before the stimulation, (+)-tubocurarine was added to prevent disturbing muscular contractions during the experimental epileptic attack.The narcotic level may have been different in the different experiments-an important point in the interpretatio...

A Proposed Common Mechanism of Action for General and Local Anaesthetics in the Central Nervous System

“…The local anaesthetics procaine and lignocaine produce analgesia by an effect on the central nervous system following intravenous administration (Wagers & Smith, 1960). Another central effect produced by both general and local anaesthetics is suppression of experimentally-induced convulsions in laboratory animals and of grand mal epileptic seizures in man (Bernhard & Bohm, 1955). Thus, local anaesthetics have a pattern of effects on the central nervous system very similar to the classical pattern of the general anaesthetics.…”

Tetrodotoxin‐induced Central Nervous System Depression

“…Tetrodotoxin, like the general and local anaesthetics, suppressed the electrical responses of isolated slabs of cerebral cortex when it was either applied directly to the cortex or given intravenously. The tetrodotoxin-induced increase in the threshold for epileptiform after-discharges, although not studied in detail, suggests that this drug might possess an anticonvulsive effect similar to that of the general and local anaesthetics (Bernhard & Bohm, 1955).…”

Experimental Epilepsy and Blood–Brain Barrier

“…Amylocaine powder sol. 5 (1) As shown in the tables, the four compounds studied are true epileptogenic agents when used intravenously at the following dose levels: amylocaine 21 and 22 mg/kg, hexylcaine starting with 10 but usually 12 mg/kg, lidocaine starting with 10 but usually 18 mg/kg and dioxone starting with 13 mg/kg.…”