Effects Of QX-314 Research Articles

The latest research of quaternary amine local anesthetic QX-314

Background Generally, long-acting local anesthetic is used for analgesia in clinic, but low concentration may lead to inefficiency and high concentration may result in the block of motor function due to individual difference. Therefore, it does not meet the need of perfect analgesic effect. Objective To summarize the recent literature about the study of QX-314. Content The quaternary amine lidocaine derivative-QX-314 with permanent positive charge, dose not permeate the membrane passively. The recent studies showed that QX-314 could penetrate into nerve cell and blocked sodium channel through the transient receptor potential vanlloid subtype 1 (TRPV1) channel, and produced prolonged analgesia effect with little effect on the motor function. Trend The analgesic effect of QX-314 indicates a new way for the clinic use of regional anesthesia. Key words: Anesthetic, local; Analgesia; QX-314; Transient receptor potential vanlloid subtype 1

The effects of QX-314 on medullary respiratory neurones

The synaptic and current-evoked responses of respiratory neurones located in the nucleus of the tractus solitarius, the para- and retroambigual regions and the nucleus ambiguus, were examined after voltage-dependent sodium currents were blocked by intracellular application of the quaternary lidocaine derivative QX-314. (1) QX-314 abolished orthodromically and antidromically evoked action potential discharge. Only antidromic action potentials recovered during negative DC current injection. (2) QX-314 did not alter the amplitude or duration of small and short excitatory and inhibitory postsynaptic potentials evoked by vagus or superior laryngeal nerve stimulation. Larger and longer waves of spontaneous membrane depolarizations, however, were slightly diminished. (3) The repetitive discharge evoked by depolarizing current pulses was blocked by QX-314. Positive current pulses produced less membrane depolarization than under control and often evoked only a single action potential at the beginning of the pulse, indicating that QX-314 interferes with the processes responsible for repetitive firing. (4) When fast spike discharges were completely blocked, positive current pulses occasionally evoked depolarizing 'spikes' and potentials which were followed by a hyperpolarization. We conclude that a noninactivating sodium inward current and calcium currents contribute to the electroresponsiveness of respiratory neurones.

The effects of QX314 on thalamic neurons

The effects of QX314 were studied in cat thalamic neurons recorded in vivo. Besides blocking Na+ spike electrogenesis, QX314 transformed spindle oscillations into a single long-lasting period of hyperpolarization that terminated with a rebound Ca2+ spike. Large sustained injections of the drug resulted in the occurrence of numerous fast prepotentials that had the characteristics of attenuated dendritic Ca2+ spikes. These effects are interpreted as resulting from the blockage by QX314 of a persistent Na+ current and a delayed rectifier K+ current which currents have already been disclosed in thalamic neurons recorded in vitro.

Sites of action and active forms of lidocaine and some derivatives on cardiac Purkinje fibers.

We have compared the effects of lidocaine (L) to those of several derivatives in an attempt to determine the sites of action and active forms of the molecules. We studied cardiac Purkinje fibers with intracellular microelectrodes, and drugs were administered by superfusion or by iontophoretic intracellular injection. We compared to L the effects of QX-314 and QX-572, two quaternary derivatives, and also compound 6603, a tertiary analogue with a pKa of 9.81. When administered by superfusion in concentrations of 10(-5) and 10(-4) M, all four agents exerted qualitatively similar effects on the transmembrane action potential. The rate of onset of action of the quaternary derivatives was considerably slower than that of L and their actions were not reversed by superfusion for 1 hour with drug-free solution. Comparison of effects of L and QX-314 after intracellular injection showed that attenuation of Vmax, and thus of the fast inward current, results from interaction of the charged form acting form acting from the inner surface of the sarcolemma. After intracellular injection, QX-314 diffused readily along the long axis of fiber bundles, and it was thus possible to expose the inner surface of a large number of contiguous cells to drug. Comparison of results of extracellular and intracellular application suggests that effects on the voltate during phase 2 result from the charged form acting from the inner surface, but effects on total action potential duration result only from drug acting from the outer surface of the sarcolemma. Unlike L, the three derivatives did not decrease the slope of normal phase 4 depolarization. The results may help relate antiarrhythmic action to specific effects on transmembrane potentials.