Potassium currents in rat cortical neurons in culture are enhanced by the antiepileptic drug carbamazepine

1990 ◽  
Vol 68 (4) ◽  
pp. 545-547 ◽  
Author(s):  
C. Zona ◽  
V. Tancredi ◽  
E. Palma ◽  
G. C. Pirrone ◽  
M. Avoli
Keyword(s):  
Antiepileptic Drug ◽  
Antiepileptic Drugs ◽  
Cortical Neurons ◽  
Potassium Currents ◽  
Patch Clamping ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
Voltage Dependent ◽  
Rat Neocortex ◽  
Rat Cortical Neurons

We report that carbamazepine (Tegretol), a drug that is useful for the treatment of complex partial seizures, enhances outward, voltage-dependent K+ currents generated by rat neocortical cells in culture and recorded with patch-clamping techniques. This effect is seen in the presence of therapeutic concentrations of carbamazepine (10–20 μM). Furthermore, at these doses carbamazepine does not influence voltage-dependent inward Na+ and Ca2+ currents recorded in these cells. The action exerted by carbamazepine on K+ currents is a novel finding and might represent an important mechanism for controlling neocortical excitability and thus the generation of epileptiform activity.Key words: potassium currents, antiepileptic drugs, carbamazepine, rat neocortex.

Interactions between tiagabine and conventional antiepileptic drugs in the rat model of complex partial seizures

2008 ◽  
Vol 115 (5) ◽  
pp. 661-667 ◽  
Author(s):  
K. K. Borowicz ◽  
M. Zadrozniak ◽  
J. J. Luszczki ◽  
S. J. Czuczwar
Keyword(s):  
Antiepileptic Drugs ◽  
Rat Model ◽  
Partial Seizures ◽  
Complex Partial Seizures

scholarly journals Effects of valproate and other antiepileptic drugs on brain glutamate, glutamine, and GABA in patients with refractory complex partial seizures

Seizure ◽  
1999 ◽  
Vol 8 (2) ◽  
pp. 120-127 ◽  
Author(s):  
O.A.C. Petroff ◽  
D.L. Rothman ◽  
K.L. Behar ◽  
F. Hyder ◽  
R.H. Mattson
Keyword(s):  
Antiepileptic Drugs ◽  
Partial Seizures ◽  
Complex Partial Seizures

scholarly journals Barbiturate-refractory epilepsy: safe schedule for therapeutic substitution

1986 ◽  
Vol 44 (3) ◽  
pp. 225-231 ◽  
Author(s):  
Ana Maria Gorz ◽  
Carlos E. S. Silvado ◽  
Paulo Rogério M. Bittencourt
Keyword(s):  
Chronic Disease ◽  
Antiepileptic Drug ◽  
Antiepileptic Drugs ◽  
Third World ◽  
Refractory Epilepsy ◽  
Serum Concentrations ◽  
Partial Seizures ◽  
First Line ◽  
Therapeutic Substitution ◽  
First Choice

Barbiturates are considered first line antiepileptic drugs in third world countries due to traditional and economic reasons. This prospective uncontrolled study of 52 patients aged 15 to 64 years (mean 24) demonstrates that patients who become refractory to barbiturates are mainly those with partial seizures with or without generalization or with a focal EEG abnormality (71%). Seizures tend to become refractory approximately 6 years after barbiturates were started. Progressive barbiturate withdrawal over a period of two to 8 months (mean 5) with institution of treatment with carbamazepine, phenytoin or sodium valproate allowed complete barbiturate withdrawal in 42 of the 52 patients (81%). Furthermore monthly seizure frequency in those in whom barbiturates were withdrawn decreased from 7.1 to 1.7 per patient. An improvement in mental status was observed but not measured. These results show that barbiturates should not be first-choice drugs in patients who have a chronic disease such as epilepsy, and indicate a schedule for barbiturate withdrawal Which is safe and independent of hospitalization or monitoring of antiepileptic drug serum concentrations.

scholarly journals Voltage-dependent block of fast chloride channels from rat cortical neurons by external tetraethylammonium ion.

1992 ◽  
Vol 100 (2) ◽  
pp. 217-231 ◽  
Author(s):  
D Y Sanchez ◽  
A L Blatz
Keyword(s):  
Ion Channels ◽  
Dose Response ◽  
Cortical Neurons ◽  
Sufficient Evidence ◽  
Dependent Manner ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Tetraethylammonium Ion ◽  
Voltage Dependent ◽  
Rat Cortical Neurons

Tetraethylammonium ion (TEA) and its longer chain derivatives have been used extensively to block currents through K-selective ion channels. Substantial information has been gained about the structure and gating mechanisms of K and other cation channels from the analysis of the blocking interactions of TEA and other quaternary ammonium ions. We now present an analysis of blocking interactions between single Cl-selective ion channels from acutely dissociated rat cortical neurons and externally applied TEA. TEA applied to the extracellular membrane surface (TEAo) blocked Cl channels in a voltage-dependent manner, with hyperpolarizing potentials favoring block. The voltage dependence of block could be adequately fit assuming that TEA enters the channel pore and binds to a site located approximately 28% of the way through the membrane electrical field. The dose-response relationship between fractional current and [TEA]o at a fixed holding potential of -40 mV was well fit to a simple model with two blocking sites with dissociation constants (Kd) of approximately 2 and 70 mM. The dose-response relationship could also be fit by a mechanism where TEA only partially blocks the channels. At the bandwidth used in these experiments (1-2 kHz), both the mean open duration (composed of the open and blocked durations) and burst duration (composed of open, blocked, and short lifetime shut durations) increased with increased [TEA]o. This is expected if TEAo can bind and unbind only when the channel is in the open kinetic state. These results suggest that the structure of the permeability pathway of these anion-selective channels may be very similar to that of other channels that are blocked by TEA. Additionally, these results caution that a blocking effect by TEA cannot, by itself, be used as sufficient evidence for implicating the participation of K channels in a particular process.

scholarly journals Cardiac Sodium Channel Blockade Due to Antiepileptic Drug Combination

2021 ◽  
Author(s):  
Ossama Maadarani ◽  
Zouheir Bitar ◽  
Abdelaziz Ashkanani ◽  
Mahmoud Elzoueiry ◽  
Mohamad Elhabibi ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Adjunctive Treatment ◽  
Channel Blockers ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
First Choice ◽  
Cardiac Sodium Channel ◽  
Voltage Dependent ◽  
Long Time ◽  
The Usa

Drugs that inhibit voltage-dependent sodium channels are commonly used to treat epilepsy. Old and novel antiepileptic drugs are used either as monotherapy or in combination to control epilepsy. For a long time, carbamazepine has been used as the first choice for the treatment of simple and complex partial seizures. In the USA, lacosamide was approved in October 2008 as an adjunctive treatment for partial-onset seizures. We describe the effect of two sodium channel blockers on the heart of a patient with epilepsy.

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