Different Sites of Membrane Action for Tetrodotoxin and Lipid-Soluble Anesthetics

1975 ◽  
Vol 53 (4) ◽  
pp. 513-524 ◽  
Author(s):  
A. L. Staiman ◽  
P. Seeman
Keyword(s):  
Benzyl Alcohol ◽  
Binding Sites ◽  
Compound Action Potential ◽  
Additive Effects ◽  
Tertiary Amines ◽  
Nerve Membrane ◽  
Membrane Action ◽  
Frog Sciatic Nerve ◽  
Membrane Binding Sites ◽  
Compound Action

1. To examine whether different local anesthetics act on different or similar sites in the nerve membrane, the effects of combinations of lipid-soluble anesthetics and tetrodotoxin (TTX) were studied on the compound action potential of the frog sciatic nerve.2. The nerve-blocking potency of TTX was potentiated 5-fold by benzyl alcohol and 10-fold by lidocaine, at concentrations of these latter two drugs which were just barely anesthetic; no such synergism occurred between saxitoxin (STX) and TTX, their combined effect being merely additive.3. Simple additive effects also occurred between benzyl alcohol and phenol, benzyl alcohol and urethane, as well as lidocaine with a spirosuccinimide, RAC 109 II.4. Synergism occurred between STX and 2-aminobenzimidazole.5. A small but consistent synergism occurred between lidocaine and benzyl alcohol.6. It is concluded that uncharged anesthetics, tertiary amines, and TTX act via different membrane binding sites which are all closely associated with the Na+ conductance channels.

Calcium Reversal of Nerve Blockade by Alcohols, Anesthetics, Tranquilizers, and Barbiturates

1974 ◽  
Vol 52 (3) ◽  
pp. 526-534 ◽  
Author(s):  
P. Seeman ◽  
S. S. Chen ◽  
M. Chau-Wong ◽  
A. Staiman
Keyword(s):  
Action Potential ◽  
Benzyl Alcohol ◽  
Phrenic Nerve ◽  
Binding Sites ◽  
Compound Action Potential ◽  
Sodium Pentobarbital ◽  
Sodium Barbital ◽  
Membrane Binding Sites ◽  
Drug Displacement ◽  
Compound Action

This study shows that Ca2+ reversed the nerve-blocking actions of procaine, lidocaine, procainamide, imipramine, chlorpromazine, tetrodotoxin, hexanol, heptanol, benzyl alcohol, thymol, sodium barbital, and sodium pentobarbital. Using the rat phrenic nerve, it was found that an elevation of external Ca2+ (from 0.22 mM to 4.4 mM) restored the blocked compound action potential of the nerve by around 30% for all three types of drugs: cationic, anionic, and uncharged.The high Ca2+ level of 4.4 mM displaced chlorpromazine from brain synaptosome membranes, but did not displace heptanol, pentobarbital, or lidocaine. Since there was no relation between blockade reversal and drug displacement by Ca2+, the data do not support the idea that Ca2+ and drugs compete for membrane-binding sites. Since approximately the same magnitude of reversal occurred with different drugs, as well as with tetrodotoxin, it is concluded that Ca2+ may cause a physiological kind of allosteric antagonism of the drug-blocked Na+ channel, or a direct augmentation of the Na+ conductance.

Effects of Static Magnetic Field on Compound Action Potential of Isolated Frog Sciatic Nerve

2019 ◽  
Vol 24 (4) ◽  
pp. 668-673
Author(s):  
Serkan Cizmeciogullari ◽  
Yasar Keskin ◽  
N. Hale Saybasili ◽  
Selcuk Paker
Keyword(s):  
Magnetic Field ◽  
Sciatic Nerve ◽  
Action Potential ◽  
Static Magnetic Field ◽  
Compound Action Potential ◽  
Frog Sciatic Nerve ◽  
Compound Action

scholarly journals Effects of Various Antiepileptics Used to Alleviate Neuropathic Pain on Compound Action Potential in Frog Sciatic Nerves: Comparison with Those of Local Anesthetics

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yuhei Uemura ◽  
Tsugumi Fujita ◽  
Sena Ohtsubo ◽  
Naomi Hirakawa ◽  
Yoshiro Sakaguchi ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Nerve Conduction ◽  
Local Anesthetics ◽  
Compound Action Potential ◽  
Receptor Activation ◽  
Nerve Fibers ◽  
Receptor Inhibition ◽  
Compound Action Potentials ◽  
Frog Sciatic Nerve ◽  
Compound Action

Antiepileptics used for treating neuropathic pain have various actions including voltage-gated Na+and Ca2+channels, glutamate-receptor inhibition, andGABAA-receptor activation, while local anesthetics are also used to alleviate the pain. It has not been fully examined yet how nerve conduction inhibitions by local anesthetics differ in extent from those by antiepileptics. Fast-conducting compound action potentials (CAPs) were recorded from frog sciatic nerve fibers by using the air-gap method. Antiepileptics (lamotrigine and carbamazepine) concentration dependently reduced the peak amplitude of the CAP (IC50=0.44and 0.50 mM, resp.). Carbamazepine analog oxcarbazepine exhibited an inhibition smaller than that of carbamazepine. Antiepileptic phenytoin (0.1 mM) reduced CAP amplitude by 15%. On the other hand, other antiepileptics (gabapentin, sodium valproate, and topiramate) at 10 mM had no effect on CAPs. The CAPs were inhibited by local anesthetic levobupivacaine (IC50=0.23 mM). These results indicate that there is a difference in the extent of nerve conduction inhibition among antiepileptics and that some antiepileptics inhibit nerve conduction with an efficacy similar to that of levobupivacaine or to those of other local anesthetics (lidocaine, ropivacaine, and cocaine) as reported previously. This may serve to know a contribution of nerve conduction inhibition in the antinociception by antiepileptics.

The Impulse-Blocking Concentrations of Anesthetics, Alcohols, Anticonvulsants, Barbiturates, and Narcotics on Phrenic and Sciatic Nerves

1974 ◽  
Vol 52 (3) ◽  
pp. 535-550 ◽  
Author(s):  
A. Staiman ◽  
P. Seeman
Keyword(s):  
Sciatic Nerve ◽  
Action Potential ◽  
Phrenic Nerve ◽  
Partition Coefficients ◽  
Compound Action Potential ◽  
Tertiary Amines ◽  
Response Curves ◽  
Acidic Drugs ◽  
Sciatic Nerves ◽  
Compound Action

(1) The nerve-blocking potencies of anesthetics, alcohols, tranquilizers, antidepressants, anticonvulsants, barbiturates, and narcotics were obtained on the rat phrenic nerve and the sciatic nerves of the frog and the rat. Skou's second method for equilibrium blockade was used, and complete dose–response curves were obtained on the height of the compound action potential.(2) Uncharged drugs (alcohols, urethane) and acidic drugs (barbiturates, diphenylhydantoin) caused half blockade of the phrenic nerve (11 μm diameter fibers) at concentrations about 25–35% of those causing half blockade of sciatic nerve (16 μm fibers).(3) Tertiary amines (procaine, spirosuccinimide enantiomers, chlorpromazine, haloperidol, trifluperidol, methadone, and naloxone) produced half blockade of the phrenic nerve at concentrations about 10% of those producing half blockade of the sciatic nerve. Frog and rat sciatic C50% block values (i.e. the drug concentration that reduced the compound action potential by 50%) were the same.(4) The phrenic C50% block value for tetrodotoxin was 7.1 times higher than that for the sciatic nerve.(5) The phrenic C50% blockvalues of the neutral and acidic drugs (together as a group) correlated inversely with the membrane/buffer partition coefficients of the drugs, in accordance with the classical Meyer–Overton rule of anesthesia. The phrenic C50% block values for the tertiary amines also correlated inversely with the membrane/buffer partition coefficients. Tetrodotoxin did not fit on these two correlations, and appeared to fall into a category of its own.(6) It was concluded that, whether comparing different nerves or the same nerve at different stages of growth, smaller myelinated fibers required lower nerve-blocking concentrations of drugs.

Interactions of Lidocaine and Calcium in Blocking the Compound Action Potential of Frog Sciatic Nerve

1984 ◽  
Vol 60 (3) ◽  
pp. 205-208 ◽  
Author(s):  
Hachiro Saito ◽  
Tomoaki Akutagawa ◽  
Luke M. Kitahata ◽  
David Stagg ◽  
J. G. Collins ◽  
...  
Keyword(s):  
Sciatic Nerve ◽  
Action Potential ◽  
Compound Action Potential ◽  
Frog Sciatic Nerve ◽  
Compound Action
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