The Experts below are selected from a list of 393 Experts worldwide ranked by ideXlab platform

Johannes Gleitz - One of the best experts on this subject based on the ideXlab platform.

  • Kavain dihydroKavain and dihydromethysticin non competitively inhibit the specific binding of 3h batrachotoxinin a 20 α benzoate to receptor site 2 of voltage gated na channels
    Planta Medica, 1998
    Co-Authors: Jutta Friese, Johannes Gleitz
    Abstract:

    The mode of action of the kava pyrones, Kavain, dihydroKavain and dihydromethysticin on the specific binding of [3H]-batrachotoxinin-A 20-α-benzoate to epitope 2 of voltage-dependent Na + channels was investigated by performing saturation experiments in the presence and absence of these kava pyrones. The tested compounds significantly decreased the apparent total number of binding sites (B max ) for [ 3 H]-batrachotoxinin-A 20-α-benzoate (control: 0.5pmol/mg protein, kava pyrones: 0.2-0.27pmol/mg protein) with little change in the equilibrium constants (K D ) for [ 3 H]-batrachotoxin-A 20-α-benzoate (control: 28.2nM, kava pyrones: 24-31 nM). The results indicate for the kava pyrones a non-competitive inhibition of the specific [3H]-batrachotoxinin-A 20-α-benzoate binding to receptor site 2 of voltage-gated Na + channels.

  • Kavain, dihydroKavain, and dihydromethysticin non-competitively inhibit the specific binding of [3H]-batrachotoxinin-A 20-alpha-benzoate to receptor site 2 of voltage-gated Na+ channels.
    Planta medica, 1998
    Co-Authors: Jutta Friese, Johannes Gleitz
    Abstract:

    The mode of action of the kava pyrones, Kavain, dihydroKavain and dihydromethysticin on the specific binding of [3H]-batrachotoxinin-A 20-alpha-benzoate to epitope 2 of voltage-dependent Na+ channels was investigated by performing saturation experiments in the presence and absence of these kava pyrones. The tested compounds significantly decreased the apparent total number of binding sites (Bmax) for [3H]-batrachotoxinin-A 20-alpha-benzoate (control: 0.5 pmol/mg protein, kava pyrones: 0.2-0.27 pmol/mg protein) with little change in the equilibrium constants (KD) for [3H]-batrachotoxin-A 20-alpha-benzoate (control: 28.2 nM, kava pyrones: 24-31 nM). The results indicate for the kava pyrones a non-competitive inhibition of the specific [3H]-batrachotoxinin-A 20-alpha-benzoate binding to receptor site 2 of voltage-gated Na+ channels.

  • [3H]-monoamine uptake inhibition properties of kava pyrones.
    Planta Medica, 1997
    Co-Authors: Ulrike Seitz, Almut Schüle, Johannes Gleitz
    Abstract:

    : Three kava pyrones, the natural compounds (+)-methysticine and (+)-Kavain, and the synthetic racemate (+/-)-Kavain, were tested concerning their action on in vitro uptake of monoamines in synaptosomes prepared from the cerebral cortex and hippocampus of rats. (+/-)-Kavain and (+)-Kavain were found to potently inhibit the uptake of [3H]-noradrenaline. Uptake of [3H]-noradrenaline was inhibited in the following order of potency: (+/-)-Kavain = (+)-Kavain > (+)-methysticine, whereas none of the kava pyrones efficiently blocked the uptake of [3H]-serotonin. The results indicate a pyrone-specific non-stereo-selective inhibition of the [3H]-noradrenaline uptake which might be responsible for or, at least, contribute to the psychotropic properties of kava pyrones.

  • relaxation of evoked contractile activity of isolated guinea pig ileum by Kavain
    Planta Medica, 1997
    Co-Authors: Ulrike Seitz, Johannes Gleitz, Angela Ameri, Helmut Pelzer, Thies Peters
    Abstract:

    : Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-Kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-Kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-Kavain (400 microM). However, (+/-)-Kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-Kavain may act in a non-specific musculotropic way on the smooth muscle membrane.

  • Relaxation of evoked contractile activity of isolated guinea-pig ileum by (±)-Kavain
    Planta Medica, 1997
    Co-Authors: Ulrike Seitz, Johannes Gleitz, Angela Ameri, Helmut Pelzer, Thies Peters
    Abstract:

    : Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-Kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-Kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-Kavain (400 microM). However, (+/-)-Kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-Kavain may act in a non-specific musculotropic way on the smooth muscle membrane.

Thies Peters - One of the best experts on this subject based on the ideXlab platform.

  • relaxation of evoked contractile activity of isolated guinea pig ileum by Kavain
    Planta Medica, 1997
    Co-Authors: Ulrike Seitz, Johannes Gleitz, Angela Ameri, Helmut Pelzer, Thies Peters
    Abstract:

    : Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-Kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-Kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-Kavain (400 microM). However, (+/-)-Kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-Kavain may act in a non-specific musculotropic way on the smooth muscle membrane.

  • Relaxation of evoked contractile activity of isolated guinea-pig ileum by (±)-Kavain
    Planta Medica, 1997
    Co-Authors: Ulrike Seitz, Johannes Gleitz, Angela Ameri, Helmut Pelzer, Thies Peters
    Abstract:

    : Kava pyrones are the pharmacologically active compounds of Piper methysticum Forst. In the present study, the effect of the synthetic kava pyrone (+/-)-Kavain was investigated on evoked contractile activity of isolated guinea-pig ileum. (+/-)-Kavain (1 microM-1 mM) dose-dependently reduced contractions of ileum evoked by carbachol (10 microM), by BAY K 8644 (0.3 microM), or by substance P (0.05 microM). (+/-)-Kavain also inhibited the contractile responses induced by raising the extracellular K+ concentration from 4 to 20 mM and by blocking the K+ channel by barium chloride (1 mM) or 4-aminopyridine (0.3 mM). After pre-incubation with 1 microM nifedipine, carbachol (1 microM) evoked 18.2 +/- 14.3% of contraction at control (i.e. prior pre-incubation with nifedipine). This remaining response was completely abolished by high concentrations of (+/-)-Kavain (400 microM). After treatment of the longitudinal ileum strips with pertussis toxin (PTX), carbachol (1 microM) evoked 27.0 +/- 6.2% of the control response in untreated ileum. These contractions were also blocked by (+/-)-Kavain (400 microM). However, (+/-)-Kavain had no effect on the caffeine-induced (20 mM) contractions of ileum strips, which were permeabilized with digitonin or beta-escin. Moreover, it failed to affect Ca(2+)-evoked contractions of skinned muscles. These results suggest that the kava pyrone (+/-)-Kavain may act in a non-specific musculotropic way on the smooth muscle membrane.

  • antithrombotic action of the kava pyrone Kavain prepared from piper methysticum on human platelets
    Planta Medica, 1997
    Co-Authors: Johannes Gleitz, A. Beile, Angela Ameri, P Wilkens, Thies Peters
    Abstract:

    (+)-Kavain, a 4-methoxy-α-pyrone prepared from Piper methysticum Forst. (Piperaceae), was investigated regarding its assumed antithrombotic action on human platelets which was deduced from its ability to suppress arachidonic acid (AA)-induced aggregation, exocytosis of ATP, and inhibition of cyclooxygenase (COX) and thromboxane synthase (TXS) activity, the latter two effects being estimated from the generation of prostaglandin E 2 (PGE 2 ) and thromboxane A 2 (TXA 2 ), respectively. Exogenously applied AA (100μmol/l) provoked a 90% aggregation of platelets, the release of 14pmol ATP, and the formation of either 220 pg TXA 2 or 43 pg PGE 2 , each parameter being related to 10 6 platelets. An application of (+)-Kavain 5 min before AA, dose-dependently diminished aggregation, ATP-release, and the synthesis of TXA 2 and PGE 2 with IC 50 values of 78, 115, 71, and 86 μmol/l, respectively. The similarity of the IC 50 values suggest an inhibition of COX by (+)-Kavain as primary target, thus suppressing the generation of TXA 2 which induces aggregation of platelets and exocytosis of ATP by its binding on TXA 2 -receptors.

  • Antithrombotic Action of the Kava Pyrone (+)-Kavain Prepared from Piper methysticum on Human Platelets*
    Planta Medica, 1997
    Co-Authors: Johannes Gleitz, Angela Ameri, P Wilkens, Beile A, Thies Peters
    Abstract:

    (+)-Kavain, a 4-methoxy-α-pyrone prepared from Piper methysticum Forst. (Piperaceae), was investigated regarding its assumed antithrombotic action on human platelets which was deduced from its ability to suppress arachidonic acid (AA)-induced aggregation, exocytosis of ATP, and inhibition of cyclooxygenase (COX) and thromboxane synthase (TXS) activity, the latter two effects being estimated from the generation of prostaglandin E 2 (PGE 2 ) and thromboxane A 2 (TXA 2 ), respectively. Exogenously applied AA (100μmol/l) provoked a 90% aggregation of platelets, the release of 14pmol ATP, and the formation of either 220 pg TXA 2 or 43 pg PGE 2 , each parameter being related to 10 6 platelets. An application of (+)-Kavain 5 min before AA, dose-dependently diminished aggregation, ATP-release, and the synthesis of TXA 2 and PGE 2 with IC 50 values of 78, 115, 71, and 86 μmol/l, respectively. The similarity of the IC 50 values suggest an inhibition of COX by (+)-Kavain as primary target, thus suppressing the generation of TXA 2 which induces aggregation of platelets and exocytosis of ATP by its binding on TXA 2 -receptors.

  • Kavain inhibits non stereospecifically veratridine activated na channels
    Planta Medica, 1996
    Co-Authors: Johannes Gleitz, Angela Ameri, Norbert Gottner, Thies Peters
    Abstract:

    : The action of the natural kava pyrone, (+)-Kavain, and its synthetic racemate, (+/-)-Kavain, on voltage-dependent Na+ channels was investigated, while considering their stereospecific properties, on veratridine-induced increases in cytosolic free Na+ and Ca2+ ([Na+]i, [Ca2+]i) and the release of endogenous glutamate from cerebrocortical synaptosomes. Both compounds dose-dependently suppressed the veratridine-induced increase in [Na+]i, [Ca2+]i and glutamate release with IC50 values (+/- S.D.) of 71 +/- 22, 72 +/- 7, 120 +/- 37 micromol/l (+)-Kavain and 77 +/- 21, 90 +/- 14, 92 +/- 23 micromol/l (+/-)-Kavain, respectively. As judged from the dose-dependency, IC50 values, velocity and time course of action, both kava pyrones were equally effective suggesting a non-stereospecific inhibition of veratridine-activated Na+ channels.

A. Beile - One of the best experts on this subject based on the ideXlab platform.

  • antithrombotic action of the kava pyrone Kavain prepared from piper methysticum on human platelets
    Planta Medica, 1997
    Co-Authors: Johannes Gleitz, A. Beile, Angela Ameri, P Wilkens, Thies Peters
    Abstract:

    (+)-Kavain, a 4-methoxy-α-pyrone prepared from Piper methysticum Forst. (Piperaceae), was investigated regarding its assumed antithrombotic action on human platelets which was deduced from its ability to suppress arachidonic acid (AA)-induced aggregation, exocytosis of ATP, and inhibition of cyclooxygenase (COX) and thromboxane synthase (TXS) activity, the latter two effects being estimated from the generation of prostaglandin E 2 (PGE 2 ) and thromboxane A 2 (TXA 2 ), respectively. Exogenously applied AA (100μmol/l) provoked a 90% aggregation of platelets, the release of 14pmol ATP, and the formation of either 220 pg TXA 2 or 43 pg PGE 2 , each parameter being related to 10 6 platelets. An application of (+)-Kavain 5 min before AA, dose-dependently diminished aggregation, ATP-release, and the synthesis of TXA 2 and PGE 2 with IC 50 values of 78, 115, 71, and 86 μmol/l, respectively. The similarity of the IC 50 values suggest an inhibition of COX by (+)-Kavain as primary target, thus suppressing the generation of TXA 2 which induces aggregation of platelets and exocytosis of ATP by its binding on TXA 2 -receptors.

  • the protective action of tetrodotoxin and Kavain on anaerobic glycolysis atp content and intracellular na and ca2 of anoxic brain vesicles
    Neuropharmacology, 1996
    Co-Authors: Johannes Gleitz, A. Beile, Claudia Tosch, Thies Peters
    Abstract:

    Abstract Because recent reports point to Na+ channel blockers as protective agents directed against anoxia-induced neuronal damage including protection of anaerobic glycolysis, the influences of tetrodotoxin (TTX) and (±)-Kavain on anoxic rat brain vesicles were investigated with respect to lactate synthesis, vesicular ATP content and cytosolic free Na+ and Ca2+ ([Na+]i, [Ca2+]i), both of the latter determined fluorometrically employing SBFI and FURA-2, respectively. After anoxia, basal lactate production was increased from 2.9 to 9.8 nmol lactate/min/mg protein. Although lactate synthesis seemed to be stable for at least 45 min of anoxia, as deduced from the linearity of lactate production, the ATP content declined continuously with a half life (τ 1 2 ) af 14.5 min, indicating that anaerobic glycolysis was insufficient to cover the energy demand of anoxic vesicles. Correspondingly, [Na+]i and [Ca2+]i increased persistently after anoxia by 22.1 mmol/l Na+ and 274.9 nmol/l Ca2+, determined 6.3 min after onset. An additional stimulation of vesicles with veratridine accelerated the drop of ATP (τ 1 2 = 5.1 min) and provoked a massive Na+ overload, which levelled off to 119 mmol/l Na+ within a few minutes. Concomitantly, [Ca2+]i increased linearly with a rate of 355 nmol Ca2+/l/min. Despite the massive perturbation of ion homeostasis, lactate production was unaffected during the first 8 min of veratridine stimulation. However, complete inhibition of lactate synthesis took place 30 min after veratridine was added. The Na+ channel blockers TTX and (±)-Kavain, if applied before anoxia, preserved vesicular ATP content, diminished anoxia-induced increases in [Na+]i and [Ca2+]i and prevented both the veratridine-induced increases of [Na+]i and [Ca2+]i and the inhibition of lactate production. The data indicate a considerable Na+ influx via voltage-dependent Na+ channels during anoxia, which speeds up the decline in ATP and provokes an increase in [Ca2+]i. A massive Na+ and Ca2+ overload induced by veratridine failed to influence lactate synthesis directly, but initiated its inhibition. © 1997 Elsevier Science Ltd. All rights reserved.

  • The protective action of tetrodotoxin and (+/-)-Kavain on anaerobic glycolysis, ATP content and intracellular Na+ and Ca2+ of anoxic brain vesicles.
    Neuropharmacology, 1996
    Co-Authors: Johannes Gleitz, A. Beile, Claudia Tosch, Thies Peters
    Abstract:

    Abstract Because recent reports point to Na+ channel blockers as protective agents directed against anoxia-induced neuronal damage including protection of anaerobic glycolysis, the influences of tetrodotoxin (TTX) and (±)-Kavain on anoxic rat brain vesicles were investigated with respect to lactate synthesis, vesicular ATP content and cytosolic free Na+ and Ca2+ ([Na+]i, [Ca2+]i), both of the latter determined fluorometrically employing SBFI and FURA-2, respectively. After anoxia, basal lactate production was increased from 2.9 to 9.8 nmol lactate/min/mg protein. Although lactate synthesis seemed to be stable for at least 45 min of anoxia, as deduced from the linearity of lactate production, the ATP content declined continuously with a half life (τ 1 2 ) af 14.5 min, indicating that anaerobic glycolysis was insufficient to cover the energy demand of anoxic vesicles. Correspondingly, [Na+]i and [Ca2+]i increased persistently after anoxia by 22.1 mmol/l Na+ and 274.9 nmol/l Ca2+, determined 6.3 min after onset. An additional stimulation of vesicles with veratridine accelerated the drop of ATP (τ 1 2 = 5.1 min) and provoked a massive Na+ overload, which levelled off to 119 mmol/l Na+ within a few minutes. Concomitantly, [Ca2+]i increased linearly with a rate of 355 nmol Ca2+/l/min. Despite the massive perturbation of ion homeostasis, lactate production was unaffected during the first 8 min of veratridine stimulation. However, complete inhibition of lactate synthesis took place 30 min after veratridine was added. The Na+ channel blockers TTX and (±)-Kavain, if applied before anoxia, preserved vesicular ATP content, diminished anoxia-induced increases in [Na+]i and [Ca2+]i and prevented both the veratridine-induced increases of [Na+]i and [Ca2+]i and the inhibition of lactate production. The data indicate a considerable Na+ influx via voltage-dependent Na+ channels during anoxia, which speeds up the decline in ATP and provokes an increase in [Ca2+]i. A massive Na+ and Ca2+ overload induced by veratridine failed to influence lactate synthesis directly, but initiated its inhibition. © 1997 Elsevier Science Ltd. All rights reserved.

  • Anticonvulsive action of (±)-Kavain estimated from its properties on stimulated synaptosomes and Na+ channel receptor sites
    European Journal of Pharmacology, 1996
    Co-Authors: Johannes Gleitz, A. Beile, Jutta Friese, Angela Ameri, Thies Peters
    Abstract:

    Abstract Kava pyrones are constituents of the intoxicating pepper (Piper methysticum Forst.), which has been shown to be anticonvulsive. The question of how the excitability of neurons is affected was investigated by determining the interaction of (±)-Kavain with epitopes (site 1, site 2) of voltage-dependent Na+ channels and the action of (±)-Kavain on 4-aminopyridine-stimulated synaptosomes as model of repetitive firing neurons. [3H]Saxitoxin and [3H]batrachotoxin were used for radioligand-binding assays performed with synaptosomal membranes. Glutamate released from 4-aminopyridine-stimulated cerebrocortical synaptosomes and the cytosolic concentrations of Na+ and Ca2+ ([Na+]i, [Ca2+]i) were detected fluorometrically by using an enzyme-linked assay, sodium-binding benzofuranisophthalate (SBFI) and Fura-2, respectively. (±)-Kavain failed to compete with [3H]saxitoxin up to 400 μmol/l but dose-dependently suppressed binding of [3H]batrachotoxin with an IC50 value of 88 μmol/l (Ki = 72 μmol/l) although displacement of [3H]batrachotoxin was restricted to 33% of control at 400 μmol/l (±)-Kavain. In stimulated synaptosomes, 5 mmol/1 4-aminopyridine provoked an increase in [Na+]i and [Ca2+]i by 9 mmol/l Na+ and 235 nmol/l Ca2+. Comparable to the reduction in [3H]batrachotoxin binding, 400 μmol/l (±)-Kavain suppressed the increase in [Na+]i and [Ca2+]i to 38 and 29% of control, respectively. Consistent with the increase in [Na+]i and [Ca2+]i, 5 mmol/l 4-aminopyridine provoked glutamate release (rate: 38 pmol/s∗mg protein) which was dose-dependently diminished to 60% of control by 400 μmol/l (±)-Kavain. KCl depolarization (40 mmol/l) provoked an increase in [Ca2+]i and glutamate release almost identical to the responses elicited by 4-aminopyridine but 400 μmol/l (±)-Kavain suppressed only the rate of glutamate release by 9% of control. The data suggest an interaction of (±)-Kavain with voltage-dependent Na+ and Ca2+ channels, thereby suppressing the 4-aminopyridine-induced increase in [Na+]i, [Ca2+]i and the release of endogenous glutamate.

  • anticonvulsive action of Kavain estimated from its properties on stimulated synaptosomes and na channel receptor sites
    European Journal of Pharmacology, 1996
    Co-Authors: Johannes Gleitz, A. Beile, Jutta Friese, Angela Ameri, Thies Peters
    Abstract:

    Abstract Kava pyrones are constituents of the intoxicating pepper (Piper methysticum Forst.), which has been shown to be anticonvulsive. The question of how the excitability of neurons is affected was investigated by determining the interaction of (±)-Kavain with epitopes (site 1, site 2) of voltage-dependent Na+ channels and the action of (±)-Kavain on 4-aminopyridine-stimulated synaptosomes as model of repetitive firing neurons. [3H]Saxitoxin and [3H]batrachotoxin were used for radioligand-binding assays performed with synaptosomal membranes. Glutamate released from 4-aminopyridine-stimulated cerebrocortical synaptosomes and the cytosolic concentrations of Na+ and Ca2+ ([Na+]i, [Ca2+]i) were detected fluorometrically by using an enzyme-linked assay, sodium-binding benzofuranisophthalate (SBFI) and Fura-2, respectively. (±)-Kavain failed to compete with [3H]saxitoxin up to 400 μmol/l but dose-dependently suppressed binding of [3H]batrachotoxin with an IC50 value of 88 μmol/l (Ki = 72 μmol/l) although displacement of [3H]batrachotoxin was restricted to 33% of control at 400 μmol/l (±)-Kavain. In stimulated synaptosomes, 5 mmol/1 4-aminopyridine provoked an increase in [Na+]i and [Ca2+]i by 9 mmol/l Na+ and 235 nmol/l Ca2+. Comparable to the reduction in [3H]batrachotoxin binding, 400 μmol/l (±)-Kavain suppressed the increase in [Na+]i and [Ca2+]i to 38 and 29% of control, respectively. Consistent with the increase in [Na+]i and [Ca2+]i, 5 mmol/l 4-aminopyridine provoked glutamate release (rate: 38 pmol/s∗mg protein) which was dose-dependently diminished to 60% of control by 400 μmol/l (±)-Kavain. KCl depolarization (40 mmol/l) provoked an increase in [Ca2+]i and glutamate release almost identical to the responses elicited by 4-aminopyridine but 400 μmol/l (±)-Kavain suppressed only the rate of glutamate release by 9% of control. The data suggest an interaction of (±)-Kavain with voltage-dependent Na+ and Ca2+ channels, thereby suppressing the 4-aminopyridine-induced increase in [Na+]i, [Ca2+]i and the release of endogenous glutamate.

Boris Ferger - One of the best experts on this subject based on the ideXlab platform.

  • neuroprotective effects of Kavain in the mptp mouse model of parkinson s disease
    Synapse, 2001
    Co-Authors: Nicole Schmidt, Boris Ferger
    Abstract:

    This is the first study to investigate the potential protective effects of the lipophilic kavapyrone (±)-Kavain in the experimental MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease (PD). Male C57BL/6 mice were treated with (±)-Kavain (50, 100, or 200 mg/kg i.p.) or vehicle 60 min before and 60 min after a single administration of MPTP (30 mg/kg s.c.) or saline, respectively. Mice were sacrificed after 7 days and the neostriatum was analyzed for dopamine and its metabolites using HPLC with electrochemical detection. Furthermore, nigral sections were processed for tyrosine hydroxylase (TH) immunocytochemistry. To determine the effects of (±)-Kavain (200 mg/kg) on MPTP metabolism, HPLC analysis of striatal MPP+ (1-methyl-4-phenylpyridinium) levels was performed. MPTP treatment alone led to a significant depletion of striatal dopamine levels to 12.61% of saline controls. The lower dosages of (±)-Kavain (50 and 100 mg/kg) showed only a nonsignificant attenuation of MPTP-induced dopamine depletion, but a high dosage of (±)-Kavain (200 mg/kg) significantly antagonized the dopamine depletion to 58.93% of saline control values. Remarkably, the MPTP-induced decrease of TH-immunoreactivity as well as the loss of nigral neurons was completely prevented by (±)-Kavain (200 mg/kg). Striatal MPP+ levels were not altered by (±)-Kavain treatment. In conclusion, we found that MPTP metabolism was not influenced by (±)-Kavain and postulate the antiglutamatergic effects of (±)-Kavain for its protective effects against MPTP toxicity. (±)-Kavain may be a novel candidate for further preclinical studies in animal models of PD and other disorders with glutamatergic overactivity. Synapse 40:47–54, 2001. © 2001 Wiley-Liss, Inc.

  • Neuroprotective effects of (±)‐Kavain in the MPTP mouse model of Parkinson's disease
    Synapse, 2001
    Co-Authors: Nicole Schmidt, Boris Ferger
    Abstract:

    This is the first study to investigate the potential protective effects of the lipophilic kavapyrone (±)-Kavain in the experimental MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease (PD). Male C57BL/6 mice were treated with (±)-Kavain (50, 100, or 200 mg/kg i.p.) or vehicle 60 min before and 60 min after a single administration of MPTP (30 mg/kg s.c.) or saline, respectively. Mice were sacrificed after 7 days and the neostriatum was analyzed for dopamine and its metabolites using HPLC with electrochemical detection. Furthermore, nigral sections were processed for tyrosine hydroxylase (TH) immunocytochemistry. To determine the effects of (±)-Kavain (200 mg/kg) on MPTP metabolism, HPLC analysis of striatal MPP+ (1-methyl-4-phenylpyridinium) levels was performed. MPTP treatment alone led to a significant depletion of striatal dopamine levels to 12.61% of saline controls. The lower dosages of (±)-Kavain (50 and 100 mg/kg) showed only a nonsignificant attenuation of MPTP-induced dopamine depletion, but a high dosage of (±)-Kavain (200 mg/kg) significantly antagonized the dopamine depletion to 58.93% of saline control values. Remarkably, the MPTP-induced decrease of TH-immunoreactivity as well as the loss of nigral neurons was completely prevented by (±)-Kavain (200 mg/kg). Striatal MPP+ levels were not altered by (±)-Kavain treatment. In conclusion, we found that MPTP metabolism was not influenced by (±)-Kavain and postulate the antiglutamatergic effects of (±)-Kavain for its protective effects against MPTP toxicity. (±)-Kavain may be a novel candidate for further preclinical studies in animal models of PD and other disorders with glutamatergic overactivity. Synapse 40:47–54, 2001. © 2001 Wiley-Liss, Inc.

  • in vivo effects of the kavapyrones dihydromethysticin and Kavain on dopamine 3 4 dihydroxyphenylacetic acid serotonin and 5 hydroxyindoleacetic acid levels in striatal and cortical brain regions
    Planta Medica, 1998
    Co-Authors: Georg Boonen, Boris Ferger, K Kuschinsky, Hanns Haberlein
    Abstract:

    The in vivo effect of a single oral dose of 100 mg (+)-dihydromethysticin/kg body weight on striatal and cortical tissue concentrations of dopamine, serotonin, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid, as well as the dopamine and serotonin turnover, was tested in rats. Additionally, other rats were fed with a (±)-Kavain containing food over a period of 78 days in order to calculate the influence of a chronic treatment with kavapyrones on the neurotransmitters. The results of the present in vivo study clearly demonstrate that neither (+)-dihydromethysticin in a high single dose, nor (±)-Kavain chronically administered, altered the dopaminergic or serotonergic tissue levels in rats significantly.

  • In vivo effects of the kavapyrones (+)-dihydromethysticin and (+/-)-Kavain on dopamine, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid levels in striatal and cortical brain regions.
    Planta medica, 1998
    Co-Authors: Georg Boonen, Boris Ferger, K Kuschinsky, Hanns Haberlein
    Abstract:

    The in vivo effect of a single oral dose of 100 mg (+)-dihydromethysticin/kg body weight on striatal and cortical tissue concentrations of dopamine, serotonin, 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid, as well as the dopamine and serotonin turnover, was tested in rats. Additionally, other rats were fed with a (+/-)-Kavain containing food over a period of 78 days in order to calculate the influence of a chronic treatment with kavapyrones on the neurotransmitters. The results of the present in vivo study clearly demonstrate that neither (+)-dihydromethysticin in a high single dose, nor (+/-)-Kavain chronically administered, altered the dopaminergic or serotonergic tissue levels in rats significantly.

  • in vivo microdialysis study of Kavain on veratridine induced glutamate release
    European Journal of Pharmacology, 1998
    Co-Authors: Boris Ferger, Georg Boonen, Hanns Haberlein, K Kuschinsky
    Abstract:

    Abstract This is the first microdialysis study to address the effects of (±)-Kavain on veratridine-induced glutamate release in freely moving rats. (±)-Kavain (100 mg/kg, p.o.) significantly reduced veratridine-induced glutamate release compared with that of vehicle-treated controls. Maximum extracellular glutamate levels were obtained 20–40 min after veratridine stimulation (500 μM, added to the perfusate). In the control group the increase was 301% and in the (±)-Kavain group the increase was significantly reduced to 219% (the basal value was 100%). These results demonstrate that (±)-Kavain reduces veratridine-induced glutamate release in vivo, which confirms previous in vitro data.

K Kuschinsky - One of the best experts on this subject based on the ideXlab platform.