The Experts below are selected from a list of 45 Experts worldwide ranked by ideXlab platform

Ryoichi Sato - One of the best experts on this subject based on the ideXlab platform.

  • Mechanism of inhibition of the Sodium current by bepridil in guinea-pig isolated ventricular cells
    British journal of pharmacology, 1995
    Co-Authors: Takahiro Nawada, Ichiro Hisatome, Yasunori Tanaka, Hiroshi Kotake, Hiroto Mashiba, Norihito Sasaki, Akira Ohtahara, Ryoichi Sato
    Abstract:

    1. Effects of bepridil, a Sodium-, calcium-, and potassium-antagonistic agent, on the Na+ current were studied by the whole cell voltage clamp technique (tip resistance = 0.5 MOhm, [Na]i and [Na]o 10 mmol l-1 at 20 degrees C). 2. Bepridil produced tonic block (Kdrest = 295.44 mumol l-1, Kdi = 1.41 mumol l-1; n = 4). 3. Bepridil (100 mumol l-1) shifted the inactivation curve in the hyperpolarization direction by 13.4 +/- 2.7 mV (n = 4) without change in the slope factor. 4. In the presence of 50 mumol l-1 bepridil, bepridil showed use-dependent block at 2 Hz, whereas changes in pulse duration did not significantly effect this use-dependent block (81% +/- 2% at 10 ms, 84% +/- 3% at 30 ms, 86% +/- 3% at 100 ms; n = 4). 5. After removal of fast inactivation of the Na+ current by 3 mmol l-1 Tosylchloramide Sodium, bepridil (50 mumol l-1) still showed use-dependent block which was independent of the holding potential. 6. The recovery time constant from the bepridil-induced use-dependent block was 0.48 s at holding potential of -100 mV and 0.51 s at holding potential of -140 mV. 7. These results indicate that bepridil could bind to the receptor in the Sodium channel through the hydrophobic and the hydrophilic pathway and leave the receptor through the hydrophobic pathway in the lipid bilayer. The binding and dissociation kinetics of this drug were shown to be fast, and the accumulation of the drug in the Sodium channel appeared to be small. Bepridil is presumed to be safe in terms of adverse effects that result from drug-accumulation in the Sodium channel.

  • Aprindine blocks the Sodium current in guinea-pig ventricular myocytes
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1991
    Co-Authors: Ryoichi Sato, Ichiro Hisatome, Yasunori Tanaka, Norito Sasaki, Hiroshi Kotake, Hiroto Mashiba, Ryo Katori
    Abstract:

    Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 µmol/l) on the Na^+ current using whole cell voltage clamp (tip resistance = 0.5 Ω, [Na]_i and_o = 10 mmol/l at 18°C). Aprindine revealed tonic block (Kd_rest = 37.7 µmol/l, Kd_i = 0.74 µmol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 ± 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 µmol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% ±3070 at 1.5 ms, 82%±6% at 20 ms, 93%±7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na^+ current by 3 mmol/l Tosylchloramide Sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = −100 mV and 5.0 s at holding potential = –140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 µmol/l aprindine showed smaller use-dependent block (14% ± 7% at 2 Hz; n = 4) comparing with either at pH 7,4 (68% ± 13%; n = 4) or at pH 8.0 (90% ±12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na^+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

  • Aprindine blocks the Sodium current in guinea-pig ventricular myocytes.
    Naunyn-Schmiedeberg's archives of pharmacology, 1991
    Co-Authors: Ryoichi Sato, Ichiro Hisatome, Yasunori Tanaka, Hiroshi Kotake, Hiroto Mashiba, Sasaki N, Ryo Katori
    Abstract:

    Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 mumol/l) on the Na+ current using whole cell voltage clamp (tip resistance = 0.5 M omega, [Na]i ando = 10 mmol/l at 18 degrees C). Aprindine revealed tonic block (Kdrest = 37.7 mumol/l, Kdi = 0.74 mumol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 +/- 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 mumol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% +/- 3% at 1.5 ms, 82% +/- 6% at 20 ms, 93% +/- 7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na+ current by 3 mmol/l Tosylchloramide Sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = -100 mV and 5.0 s at holding potential = -140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 mumol/l aprindine showed smaller use-dependent block (14% +/- 7% at 2 Hz; n = 4) comparing with either at pH 7.4 (68% +/- 13%; n = 4) or at pH 8.0 (90% +/- 12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

Ryo Katori - One of the best experts on this subject based on the ideXlab platform.

  • Aprindine blocks the Sodium current in guinea-pig ventricular myocytes
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1991
    Co-Authors: Ryoichi Sato, Ichiro Hisatome, Yasunori Tanaka, Norito Sasaki, Hiroshi Kotake, Hiroto Mashiba, Ryo Katori
    Abstract:

    Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 µmol/l) on the Na^+ current using whole cell voltage clamp (tip resistance = 0.5 Ω, [Na]_i and_o = 10 mmol/l at 18°C). Aprindine revealed tonic block (Kd_rest = 37.7 µmol/l, Kd_i = 0.74 µmol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 ± 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 µmol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% ±3070 at 1.5 ms, 82%±6% at 20 ms, 93%±7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na^+ current by 3 mmol/l Tosylchloramide Sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = −100 mV and 5.0 s at holding potential = –140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 µmol/l aprindine showed smaller use-dependent block (14% ± 7% at 2 Hz; n = 4) comparing with either at pH 7,4 (68% ± 13%; n = 4) or at pH 8.0 (90% ±12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na^+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

  • Aprindine blocks the Sodium current in guinea-pig ventricular myocytes.
    Naunyn-Schmiedeberg's archives of pharmacology, 1991
    Co-Authors: Ryoichi Sato, Ichiro Hisatome, Yasunori Tanaka, Hiroshi Kotake, Hiroto Mashiba, Sasaki N, Ryo Katori
    Abstract:

    Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 mumol/l) on the Na+ current using whole cell voltage clamp (tip resistance = 0.5 M omega, [Na]i ando = 10 mmol/l at 18 degrees C). Aprindine revealed tonic block (Kdrest = 37.7 mumol/l, Kdi = 0.74 mumol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 +/- 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 mumol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% +/- 3% at 1.5 ms, 82% +/- 6% at 20 ms, 93% +/- 7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na+ current by 3 mmol/l Tosylchloramide Sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = -100 mV and 5.0 s at holding potential = -140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 mumol/l aprindine showed smaller use-dependent block (14% +/- 7% at 2 Hz; n = 4) comparing with either at pH 7.4 (68% +/- 13%; n = 4) or at pH 8.0 (90% +/- 12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

Hiroshi Kotake - One of the best experts on this subject based on the ideXlab platform.

  • Mechanism of inhibition of the Sodium current by bepridil in guinea-pig isolated ventricular cells
    British journal of pharmacology, 1995
    Co-Authors: Takahiro Nawada, Ichiro Hisatome, Yasunori Tanaka, Hiroshi Kotake, Hiroto Mashiba, Norihito Sasaki, Akira Ohtahara, Ryoichi Sato
    Abstract:

    1. Effects of bepridil, a Sodium-, calcium-, and potassium-antagonistic agent, on the Na+ current were studied by the whole cell voltage clamp technique (tip resistance = 0.5 MOhm, [Na]i and [Na]o 10 mmol l-1 at 20 degrees C). 2. Bepridil produced tonic block (Kdrest = 295.44 mumol l-1, Kdi = 1.41 mumol l-1; n = 4). 3. Bepridil (100 mumol l-1) shifted the inactivation curve in the hyperpolarization direction by 13.4 +/- 2.7 mV (n = 4) without change in the slope factor. 4. In the presence of 50 mumol l-1 bepridil, bepridil showed use-dependent block at 2 Hz, whereas changes in pulse duration did not significantly effect this use-dependent block (81% +/- 2% at 10 ms, 84% +/- 3% at 30 ms, 86% +/- 3% at 100 ms; n = 4). 5. After removal of fast inactivation of the Na+ current by 3 mmol l-1 Tosylchloramide Sodium, bepridil (50 mumol l-1) still showed use-dependent block which was independent of the holding potential. 6. The recovery time constant from the bepridil-induced use-dependent block was 0.48 s at holding potential of -100 mV and 0.51 s at holding potential of -140 mV. 7. These results indicate that bepridil could bind to the receptor in the Sodium channel through the hydrophobic and the hydrophilic pathway and leave the receptor through the hydrophobic pathway in the lipid bilayer. The binding and dissociation kinetics of this drug were shown to be fast, and the accumulation of the drug in the Sodium channel appeared to be small. Bepridil is presumed to be safe in terms of adverse effects that result from drug-accumulation in the Sodium channel.

  • Aprindine blocks the Sodium current in guinea-pig ventricular myocytes
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1991
    Co-Authors: Ryoichi Sato, Ichiro Hisatome, Yasunori Tanaka, Norito Sasaki, Hiroshi Kotake, Hiroto Mashiba, Ryo Katori
    Abstract:

    Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 µmol/l) on the Na^+ current using whole cell voltage clamp (tip resistance = 0.5 Ω, [Na]_i and_o = 10 mmol/l at 18°C). Aprindine revealed tonic block (Kd_rest = 37.7 µmol/l, Kd_i = 0.74 µmol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 ± 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 µmol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% ±3070 at 1.5 ms, 82%±6% at 20 ms, 93%±7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na^+ current by 3 mmol/l Tosylchloramide Sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = −100 mV and 5.0 s at holding potential = –140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 µmol/l aprindine showed smaller use-dependent block (14% ± 7% at 2 Hz; n = 4) comparing with either at pH 7,4 (68% ± 13%; n = 4) or at pH 8.0 (90% ±12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na^+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

  • Aprindine blocks the Sodium current in guinea-pig ventricular myocytes.
    Naunyn-Schmiedeberg's archives of pharmacology, 1991
    Co-Authors: Ryoichi Sato, Ichiro Hisatome, Yasunori Tanaka, Hiroshi Kotake, Hiroto Mashiba, Sasaki N, Ryo Katori
    Abstract:

    Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 mumol/l) on the Na+ current using whole cell voltage clamp (tip resistance = 0.5 M omega, [Na]i ando = 10 mmol/l at 18 degrees C). Aprindine revealed tonic block (Kdrest = 37.7 mumol/l, Kdi = 0.74 mumol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 +/- 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 mumol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% +/- 3% at 1.5 ms, 82% +/- 6% at 20 ms, 93% +/- 7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na+ current by 3 mmol/l Tosylchloramide Sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = -100 mV and 5.0 s at holding potential = -140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 mumol/l aprindine showed smaller use-dependent block (14% +/- 7% at 2 Hz; n = 4) comparing with either at pH 7.4 (68% +/- 13%; n = 4) or at pH 8.0 (90% +/- 12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

Hiroto Mashiba - One of the best experts on this subject based on the ideXlab platform.

  • Mechanism of inhibition of the Sodium current by bepridil in guinea-pig isolated ventricular cells
    British journal of pharmacology, 1995
    Co-Authors: Takahiro Nawada, Ichiro Hisatome, Yasunori Tanaka, Hiroshi Kotake, Hiroto Mashiba, Norihito Sasaki, Akira Ohtahara, Ryoichi Sato
    Abstract:

    1. Effects of bepridil, a Sodium-, calcium-, and potassium-antagonistic agent, on the Na+ current were studied by the whole cell voltage clamp technique (tip resistance = 0.5 MOhm, [Na]i and [Na]o 10 mmol l-1 at 20 degrees C). 2. Bepridil produced tonic block (Kdrest = 295.44 mumol l-1, Kdi = 1.41 mumol l-1; n = 4). 3. Bepridil (100 mumol l-1) shifted the inactivation curve in the hyperpolarization direction by 13.4 +/- 2.7 mV (n = 4) without change in the slope factor. 4. In the presence of 50 mumol l-1 bepridil, bepridil showed use-dependent block at 2 Hz, whereas changes in pulse duration did not significantly effect this use-dependent block (81% +/- 2% at 10 ms, 84% +/- 3% at 30 ms, 86% +/- 3% at 100 ms; n = 4). 5. After removal of fast inactivation of the Na+ current by 3 mmol l-1 Tosylchloramide Sodium, bepridil (50 mumol l-1) still showed use-dependent block which was independent of the holding potential. 6. The recovery time constant from the bepridil-induced use-dependent block was 0.48 s at holding potential of -100 mV and 0.51 s at holding potential of -140 mV. 7. These results indicate that bepridil could bind to the receptor in the Sodium channel through the hydrophobic and the hydrophilic pathway and leave the receptor through the hydrophobic pathway in the lipid bilayer. The binding and dissociation kinetics of this drug were shown to be fast, and the accumulation of the drug in the Sodium channel appeared to be small. Bepridil is presumed to be safe in terms of adverse effects that result from drug-accumulation in the Sodium channel.

  • Aprindine blocks the Sodium current in guinea-pig ventricular myocytes
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1991
    Co-Authors: Ryoichi Sato, Ichiro Hisatome, Yasunori Tanaka, Norito Sasaki, Hiroshi Kotake, Hiroto Mashiba, Ryo Katori
    Abstract:

    Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 µmol/l) on the Na^+ current using whole cell voltage clamp (tip resistance = 0.5 Ω, [Na]_i and_o = 10 mmol/l at 18°C). Aprindine revealed tonic block (Kd_rest = 37.7 µmol/l, Kd_i = 0.74 µmol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 ± 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 µmol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% ±3070 at 1.5 ms, 82%±6% at 20 ms, 93%±7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na^+ current by 3 mmol/l Tosylchloramide Sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = −100 mV and 5.0 s at holding potential = –140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 µmol/l aprindine showed smaller use-dependent block (14% ± 7% at 2 Hz; n = 4) comparing with either at pH 7,4 (68% ± 13%; n = 4) or at pH 8.0 (90% ±12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na^+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

  • Aprindine blocks the Sodium current in guinea-pig ventricular myocytes.
    Naunyn-Schmiedeberg's archives of pharmacology, 1991
    Co-Authors: Ryoichi Sato, Ichiro Hisatome, Yasunori Tanaka, Hiroshi Kotake, Hiroto Mashiba, Sasaki N, Ryo Katori
    Abstract:

    Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 mumol/l) on the Na+ current using whole cell voltage clamp (tip resistance = 0.5 M omega, [Na]i ando = 10 mmol/l at 18 degrees C). Aprindine revealed tonic block (Kdrest = 37.7 mumol/l, Kdi = 0.74 mumol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 +/- 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 mumol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% +/- 3% at 1.5 ms, 82% +/- 6% at 20 ms, 93% +/- 7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na+ current by 3 mmol/l Tosylchloramide Sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = -100 mV and 5.0 s at holding potential = -140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 mumol/l aprindine showed smaller use-dependent block (14% +/- 7% at 2 Hz; n = 4) comparing with either at pH 7.4 (68% +/- 13%; n = 4) or at pH 8.0 (90% +/- 12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

Yasunori Tanaka - One of the best experts on this subject based on the ideXlab platform.

  • Mechanism of inhibition of the Sodium current by bepridil in guinea-pig isolated ventricular cells
    British journal of pharmacology, 1995
    Co-Authors: Takahiro Nawada, Ichiro Hisatome, Yasunori Tanaka, Hiroshi Kotake, Hiroto Mashiba, Norihito Sasaki, Akira Ohtahara, Ryoichi Sato
    Abstract:

    1. Effects of bepridil, a Sodium-, calcium-, and potassium-antagonistic agent, on the Na+ current were studied by the whole cell voltage clamp technique (tip resistance = 0.5 MOhm, [Na]i and [Na]o 10 mmol l-1 at 20 degrees C). 2. Bepridil produced tonic block (Kdrest = 295.44 mumol l-1, Kdi = 1.41 mumol l-1; n = 4). 3. Bepridil (100 mumol l-1) shifted the inactivation curve in the hyperpolarization direction by 13.4 +/- 2.7 mV (n = 4) without change in the slope factor. 4. In the presence of 50 mumol l-1 bepridil, bepridil showed use-dependent block at 2 Hz, whereas changes in pulse duration did not significantly effect this use-dependent block (81% +/- 2% at 10 ms, 84% +/- 3% at 30 ms, 86% +/- 3% at 100 ms; n = 4). 5. After removal of fast inactivation of the Na+ current by 3 mmol l-1 Tosylchloramide Sodium, bepridil (50 mumol l-1) still showed use-dependent block which was independent of the holding potential. 6. The recovery time constant from the bepridil-induced use-dependent block was 0.48 s at holding potential of -100 mV and 0.51 s at holding potential of -140 mV. 7. These results indicate that bepridil could bind to the receptor in the Sodium channel through the hydrophobic and the hydrophilic pathway and leave the receptor through the hydrophobic pathway in the lipid bilayer. The binding and dissociation kinetics of this drug were shown to be fast, and the accumulation of the drug in the Sodium channel appeared to be small. Bepridil is presumed to be safe in terms of adverse effects that result from drug-accumulation in the Sodium channel.

  • Aprindine blocks the Sodium current in guinea-pig ventricular myocytes
    Naunyn-Schmiedeberg's Archives of Pharmacology, 1991
    Co-Authors: Ryoichi Sato, Ichiro Hisatome, Yasunori Tanaka, Norito Sasaki, Hiroshi Kotake, Hiroto Mashiba, Ryo Katori
    Abstract:

    Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 µmol/l) on the Na^+ current using whole cell voltage clamp (tip resistance = 0.5 Ω, [Na]_i and_o = 10 mmol/l at 18°C). Aprindine revealed tonic block (Kd_rest = 37.7 µmol/l, Kd_i = 0.74 µmol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 ± 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 µmol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% ±3070 at 1.5 ms, 82%±6% at 20 ms, 93%±7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na^+ current by 3 mmol/l Tosylchloramide Sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = −100 mV and 5.0 s at holding potential = –140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 µmol/l aprindine showed smaller use-dependent block (14% ± 7% at 2 Hz; n = 4) comparing with either at pH 7,4 (68% ± 13%; n = 4) or at pH 8.0 (90% ±12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na^+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.

  • Aprindine blocks the Sodium current in guinea-pig ventricular myocytes.
    Naunyn-Schmiedeberg's archives of pharmacology, 1991
    Co-Authors: Ryoichi Sato, Ichiro Hisatome, Yasunori Tanaka, Hiroshi Kotake, Hiroto Mashiba, Sasaki N, Ryo Katori
    Abstract:

    Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 mumol/l) on the Na+ current using whole cell voltage clamp (tip resistance = 0.5 M omega, [Na]i ando = 10 mmol/l at 18 degrees C). Aprindine revealed tonic block (Kdrest = 37.7 mumol/l, Kdi = 0.74 mumol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 +/- 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 mumol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% +/- 3% at 1.5 ms, 82% +/- 6% at 20 ms, 93% +/- 7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na+ current by 3 mmol/l Tosylchloramide Sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = -100 mV and 5.0 s at holding potential = -140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 mumol/l aprindine showed smaller use-dependent block (14% +/- 7% at 2 Hz; n = 4) comparing with either at pH 7.4 (68% +/- 13%; n = 4) or at pH 8.0 (90% +/- 12%; n = 4). The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na+ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule.