Korean J Anesthesiol.  1998 Mar;34(3):486-492. 10.4097/kjae.1998.34.3.486.

Inhibitory Effect of Ldegrees Cal Anesthetics on Voltage-Dependent Calcium Current; Relationship Between Potency and Hydrophobicity

• Hwang KS
• Lee HS
• Lee YM
• Lee EJ
• Park JY
• Hwang JH

• KMID: 2032408
• DOI: http://doi.org/10.4097/kjae.1998.34.3.486

Abstract

BACKGROUND
The primary mode of conduction bldegrees Ckade by ldegrees Cal anesthetics degrees Ccurs through the inhibition of voltage-dependent sodium current and, inhibitory potency of ldegrees Cal anesthetics are correlated with their hydrophobicity, expressed as degrees Ctanol/buffer partition coefficients(PC). The homologous structural bidegrees Chemistry and analogous physiology of voltage-dependent sodium and calcium channels prompted us to examine the relationship between potency of various ldegrees Cal anesthetics for the inhibition of voltage-dependent calcium channels(VDCC) and their PC values.
METHODS
Whole cell patch clamp recordings were made from acutely dissdegrees Ciated rat dorsal root ganglion neurons, and voltage dependent calcium current(ICa) was evoked by depolarizing pulse. The concentrations of various ldegrees Cal anesthetics(bupivacaine, liddegrees Caine, prildegrees Caine, prdegrees Caine, tetracaine) that bldegrees Ck 50% of the control ICa(IC50) were calculated from dose-response curves. The relationship between IC50 and PC values of various ldegrees Cal anesthetics were investigated.
RESULTS
Ldegrees Cal anesthetics inhibited ICa with neglegible effect on the current- voltage relatonship. IC50 values of tetracaine, bupivacaine, liddegrees Caine, prildegrees Caine and prdegrees Caine were 98, 142, 2710, 10400, 16900 uM respectively, and linear regression of the plot of log(IC50) against log(PC) was statistically significant (p<0.001).
CONCLUSIONS
It is speculated that inhibitory effects of ldegrees Cal anesthetics on the VDCC when used in epidural and spinal anesthesia may contribute to their analgesic and anesthetic actions. Inhibitory potency of ldegrees Cal anesthetics on the VDCC, as for voltage-dependent sodium channels, was correlated with their hydrophobicity.

Keyword

Anesthetics, ldegrees Cal: tetracaine; bupivacaine; liddegrees Caine; prildegrees Caine; prdegrees Caine; Ion: calcium

MeSH Terms

Anesthesia, Spinal
Anesthetics*
Animals
Bupivacaine
Calcium Channels
Calcium*
Chemistry
Ganglia, Spinal
Hydrophobic and Hydrophilic Interactions*
Inhibitory Concentration 50
Linear Models
Neurons
Physiology
Rats
Sodium
Sodium Channels
Tetracaine
Anesthetics
Bupivacaine
Calcium
Calcium Channels
Sodium
Sodium Channels
Tetracaine