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J M Langosch

Publications and source records attributed to J M Langosch.

17 recordsLinked to original sources
PubMed2006

[Psychotropic drug-induced change of weight: a review].

OBJECTIVE: The purpose of this study is to give a systematic review of change of weight associated with commonly used psychotropic drugs. METHODS: Mainly based on a MEDLINE-supported review until April 2005, data from clinical studies with antidepressants, anticonvulsants, mood stabilizers and neuroleptics were scanned for change of weight during treatment. RESULTS: Among antidepressants amitryptiline and nortriptyline have the highest incidence of weight gain followed by imipramine. Maprotiline and mirtazapine have an intermediate weight increasing potential. SSRI (except paroxetine) and MAOI had no or only slight weight inducing effects. In contrary, bupropion was associated with weight reduction. Regarding mood stabilizers and anticonvulsants, a marked gain in weight with lithium and sodium valproate was reported frequently. With gabapentin and vigabatrin a slight to moderate gain in weight was found. Minor changes of weight were found with carbamazepine and lamotrigine. Treatment with topiramate and felbamate reportedly lead to weight loss. The atypical neuroleptics clozapine and olanzapine were frequently related to a strong gain in weight followed by risperidone. Quetiapine has intermediate effects. Stable weight was found with aripiprazole and ziprasidone. A gain in weight is less frequent with older/typical neuroleptics. CONCLUSION: Beside some methodological restrictions like inconsistent information of weight changes (e. g. percent vs. mass) and the small sample of available long term studies, this review specifies the incidence of weight changes for commonly used psychotropic drugs and might be helpful to look for alternatives.

Animals↗
PubMed2005

Mirtazapine increases cortical excitability in healthy controls and epilepsy patients with major depression.

BACKGROUND: Epilepsy is often complicated by depression requiring antidepressant treatment. Such treatment might be proconvulsive. OBJECTIVE: To examine the effects of the noradrenergic and specific serotonergic antidepressant mirtazapine on motor cortex excitability in epilepsy patients with depression and in healthy controls, using transcranial magnetic stimulation (TMS). METHODS: Seven clinically depressed epilepsy patients treated with anticonvulsant drugs and six healthy volunteers were studied. Before intake of mirtazapine and 24 hours afterwards (and also three weeks afterwards in the patients), the active and resting motor threshold (AMT, RMT), the size of the motor evoked potential (MEP), the cortical silent period (SP), and intracortical inhibition/facilitation and intracortical facilitatory I wave interactions were determined using single and paired pulse TMS. RESULTS: At baseline, AMT and RMT were higher (p = 0.049 and p = 0.04, respectively) and the ratio SP duration/MEP area greater in patients (p = 0.041). In patients but not in healthy subjects AMT was lower 24 hours after intake of mirtazapine (p = 0.028). Mirtazapine had no significant effect on the MEP size, duration of the SP, or the ratio of SP duration to MEP size in patients. The duration of the SP was longer (p = 0.037) but the ratio of SP duration to MEP size remained similar in healthy subjects after mirtazapine. There were no significant differences in paired pulse measures between the two groups either at baseline or after mirtazapine. CONCLUSIONS: Mirtazapine increased neuronal excitability of pyramidal tract axons in an activated state in both healthy controls and epilepsy patients with major depression.

Adult↗
PubMed2004

Event-related potential correlates selectively reflect cognitive dysfunction in schizophrenics.

UNLABELLED: Schizophrenics show event-related potential (ERP) and particularly P3 abnormalities. To study the more detailed relationships between these ERP alterations and cognitive dysfunction we recorded and analyzed ERPs using a particular experimental approach. In 34 schizophrenics and 25 controls ERPs were obtained by a visual Go/Nogo task requiring response inhibition and were decomposed into temporally independent topographical components using Independent Component Analysis (ICA). ICA disentangled different subcomponents of P3. Subcomponent P3b with a parietal maximum amplitude was significantly reduced in the schizophrenics, probably reflecting their attentional deficits. Subcomponent P3ng with a frontal maximum amplitude and enhanced during Nogo condition appeared as an electrophysiological index of response inhibition. A significantly reduced P3ng enhancement, found in schizophrenics, probably reflects their impaired response control. CONCLUSIONS: ICA can successfully identify ERP subcomponents with distinct scalp topographies representing significant differential indices of normal and abnormal cognitive processing. Involvement of frontal brain areas in disturbed executive control in schizophrenics is supported by our ICA findings.

Adult↗
PubMed2002

Epilepsy, psychosis and clozapine.

Six patients with epilepsy and severe psychosis were treated with the atypical antipsychotic clozapine. The use of clozapine might be complicated in epileptic patients because of an increased risk of seizures. However, none of the reported patients had an increase of their seizure frequency, in contrast, three patients had a substantial reduction of seizures. One patient had a reduction of non-epileptic seizures as well. In the second part of this paper, combinations of clozapine with newer and older anticonvulsants as well as their interactions and associated risks are discussed.

Adult↗
PubMed2001

Effects of Hypericum perforatum L. on evoked potentials in guinea pig hippocampal slices.

Therapeutic uses of Hypericum extracts have been demonstrated as safe and effective in treating mild to moderate depression in numerous clinical trials. To date, however, no definitive statements on their mode of action can be made, and little information on their electrophysiological effects is available. The present communication summarises the results of our efforts directed towards clarifying the effects of an ethanolic Hypericum extract (HYP) and its hydrosoluble fraction (HYPWS), and two of its constituents hypericin and hyperforin on electrically evoked population spikes in guinea pig hippocampal slices. In higher concentrations (>10 microM), the two extract constituents tested revealed inhibitory effects only, whereas concentration-dependent (between 10(-6) to 10(-4) g/l) excitatory effects were observed for HYP and HYPWS. The excitatory effects were strongly amplified by the GABA(B) antagonist phaclofen, whereas the effects of bicucullin, a GABA(A) antagonist, were marginal. The excitations were completely blocked by the AMPA antagonist CNQX, but not by the NMDA antagonists APV and MK801 or the L-type calcium-channel blocker verapamil. This kind of excitatory effect on the hippocampus is unknown in other antidepressants and; indeed, many of the latter reduce neuronal excitability. We conclude, therefore, that the mechanisms involved in the antidepressant activity of Hypericum extracts are different from those of conventional antidepressants, and that identifying their excitatory components may facilitate their more rational standardisation.

2-Amino-5-phosphonovalerate↗
PubMed2000

Effects of lamotrigine on field potentials and long-term potentiation in guinea pig hippocampal slices.

PURPOSE: To investigate the effects of lamotrigine (LTG), a new anticonvulsant, on neuronal excitability, synaptic transmission, and long-term potentiation (LTP) in guinea pig hippocampal slices. METHODS: Electrically evoked field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) were investigated in the CA1 region of the hippocampus. RESULTS: The concentration-response curves showed different actions of LTG in concentrations near therapeutic plasma levels (10 microM) on fEPSPs and PSs. The initial slopes of fEPSPs were not affected, whereas the amplitudes of PSs were significantly decreased. Higher concentrations of LTG decreased both fEPSP slopes and PS amplitudes; however, the effects on PSs were much stronger. Also, there were no differences in fEPSP slopes or PS amplitudes compared with controls when LTP was induced in the presence of LTG (10 microM). CONCLUSIONS: Our data are in contrast to previous findings that suggest LTG acts primarily on presynaptic sites by blocking the release of excitatory amino acids. Further, LTP was not affected by LTG.

Animals↗
PubMed2000

New insights into the mechanisms and sites of action of lamotrigine.

This study was aimed at investigating the effects of lamotrigine (LTG) on electrically evoked field excitatory postsynaptic potentials (fEPSP) and population spikes in the CA1 hippocampal region of guinea pigs. The concentration response curves showed different actions of LTG on fEPSP and on population spikes. The data are in contrast to previous findings that suggest the drug acts primarily on presynaptic sites via a blockade of the release of excitatory amino acids. In the range of therapeutic plasma levels, synaptic transmission was not affected.

Animals↗
PubMed1999

Effects of (+/-)-kavain on voltage-activated inward currents of dorsal root ganglion cells from neonatal rats.

Kava pyrones extracted from pepper Piper methysticum are pharmacologically active compounds. Since kava pyrones exhibit anticonvulsive, analgesic and centrally muscle relaxing properties, the influence of a synthetic kava pyrone, (+/-)-kavain, on voltage-dependent ion channel currents was studied. Effects of (+/-)-kavain on voltage-activated inward currents were analysed in cultured dorsal root ganglion cells derived from neonatal rats. Voltage-activated Ca2+ and Na+ currents were elicited in the whole-cell configuration of the patch clamp technique. Extracellularly applied (+/-)-kavain dissolved in hydrous salt solutions reduced voltage-activated Ca2+ and Na+ channel currents within 3-5 min. As the solubility of (+/-)-kavain in hydrous solutions is low, dimethyl sulfoxide (DMSO) was added to the saline as a solvent for the drug in most experiments. When (+/-)-kavain was dissolved in DMSO, the drug induced a fast and pronounced reduction of both Ca2+ and Na+ currents, which partly recovered within 2-5 min even in the presence of the drug. The present study indicates that (+/-)-kavain reduces currents through voltage-activated Na+ and Ca2+ channels.

Animals↗
PubMed1999

Effects of carbamazepine and valproate on haloperidol plasma levels and on psychopathologic outcome in schizophrenic patients.

The objective of this study was to compare the effects of carbamazepine (CBZ) and valproate (VPA) cotreatment on the plasma levels of haloperidol and on the psychopathologic outcome in schizophrenic disorders. In this controlled clinical trial, 27 patients with an ICD-10 diagnosis of schizophrenia (N = 24) or schizoaffective disorder (N = 3) were randomly assigned to receive 4 weeks of treatment with either haloperidol alone, haloperidol with CBZ, or haloperidol with VPA. Whereas the haloperidol dose remained stable, the antiepileptic drug doses were adjusted to achieve therapeutic plasma levels. Clinical state was rated by the Positive subscale of the Positive and Negative Syndrome Scale and the Inpatient Multidimensional Psychiatric Scale. The use of CBZ was associated with significantly lower haloperidol plasma levels and with a worse clinical outcome compared with antipsychotic monotherapy. VPA had no significant effect on either plasma levels or on psychopathology. Our results suggest that comedication with haloperidol and CBZ is associated with a high risk for treatment failure. This might be a result of a pharmacokinetic interaction on the hepatic level. The concomitant use of VPA with neuroleptic therapy is not impaired by clinically significant drug interactions, but it is not associated with a better outcome under our conditions.

Adult↗
PubMed1998

Effects of the atypical antidepressant trimipramine on field potentials in the low Mg2+-model in guinea pig hippocampal slices.

Trimipramine has been classified as an atypical tricyclic antidepressant, because only weak inhibitory effects on serotonin and/or noradrenaline reuptake have been found. Since some antidepressive drugs (e.g. imipramine) and other agents used in the treatment of affective disorders (e.g. carbamazepine) modulate neuronal calcium channels, trimipramine was tested on field potential changes (fp) in the low Mg2+-model of epilepsy which has been shown to be affected by calcium antagonists. Trimipramine reduced the frequency of occurrence of fp in a dose dependent manner (5-100 microM). The threshold concentration of trimipramine which did not decrease the firing rate was approximately 1 microM. Simultaneous application of subthreshold concentrations (2 microM) of the organic calcium antagonist verapamil with trimipramine decreased the firing rate to 37.0+/-22.7% (means+/-SEM, n=7) with respect to baseline values. In contrast, no additive effects of N-methyl-D-aspartate antagonists and trimipramine were observed. In conclusion, the data suggests that the antidepressive effects observed with trimipramine treatment may be due to its inhibitory action on neuronal calcium channels.

2-Amino-5-phosphonovalerate↗
PubMed1998

The influence of (+/-)-kavain on population spikes and long-term potentiation in guinea pig hippocampal slices.

Little is known about the mechanisms of action of kava pyrones which are the pharmacological active compounds of the plant Piper methysticum Forst. We investigated the effects of the synthetic kava pyrone (+/-)-kavain on long-term potentiation (LTP) in the CA1-region of guinea pig hippocampal slices. (+/-)-Kavain reduced the amplitudes of extracellular field potential changes evoked by electrical stimulation in a concentration dependent manner. These effects were reversible. In experiments with LTP no changes were found in the presence of (+/-)-kavain. In conclusion, our findings suggest (+/-)-kavain to be an effective drug in modulating excitatory signals in the hippocampus of guinea pigs. Additionally, no alterations on synaptic plasticity in hippocampal neurons for this kava pyrone can be presumed.

Action Potentials↗
PubMed1998

[Adjuvant treatment of schizophrenic illness with carbamazepine].

Very few controlled clinical trials have been assessing the interaction of antipsychotics and antiepileptics. However, schizophrenic patients frequently receive a combination therapy consisting of haloperidol and carbamazepine. The data for this treatment strategy are contradictory and may depend on the initial plasma concentration of the antipsychotic. There is convincing evidence that after addition of carbamazepine the plasma concentration of neuroleptics drops due to hepatic enzyme induction. In this study, we treated 18 schizophrenic patients either with haloperidol alone or in combination with carbamazepine. The use of carbamazepine was associated with a dramatic fall in haloperidol plasma levels and a worse clinical outcome compared to the monotherapy group. These results, together with a review of the literature, lead us to the conclusion that there are no obvious advantages of carbamazepine co-medication in schizophrenia compared to an optimized neuroleptic monotherapy.

Anticonvulsants↗
PubMed1998

[Calcium antagonistic actions of drugs used in treatment of affective disorders].

Disturbances of intra- and extracellular calcium levels are often reported during the course of affective disorders. In this review calcium antagonistic properties of drugs used in the treatment of affective disorders are discussed. The effects of calcium channel blockers in animal models of depression and in clinical trials are compared to established treatment strategies. Knowledge on changes in calcium homoeostasis during the treatment of affective disorders may increase the scope of therapeutic options.

Animals↗
PubMed1994

Characterization and possible function of adenosine 5'-triphosphate receptors in activated rat microglia.

1. Purinoceptor agonist-induced currents in untreated (proliferating) and lipopolysaccharide (LPS; 100 ng ml-1)-treated (non-proliferating) rat microglial cells in culture were recorded by the whole-cell patch-clamp technique. These cells have two preferred resting membrane potentials, one at -35 mV and another one at -70 mV. 2. Most experiments were carried out in non-proliferating cells. ATP, ATP-gamma-S and alpha,beta-MeATP (1-1000 microM in all cases) evoked an inward current at a holding potential of -70 mV, followed, in some experiments, by an outward current. At -70 mV 2-methylthio ATP (1-1000 microM) evoked an inward current, whereas at -35 mV it produced an outward current only. 3. When K+ was replaced in the pipette solution by an equimolar concentration of Cs+ (150 mM), the main outward component of the ATP-gamma-S (10 microM) induced response disappeared. Instead, an inward current was obtained. Replacement of K+ by Cs+ did not affect the inward current evoked by 2-methylthio ATP (300 microM). 4-Aminopyridine (1-10 mM), however, almost abolished this current and unmasked a smaller outward current. 4. The rank order of agonist potency was 2-methylthio ATP > ATP > alpha,beta-MeATP. Adenosine and UTP were inactive. Suramin (300 microM) and reactive blue 2 (50 microM) antagonized the effect of 2-methylthio ATP (300 microM). 5. I-V relations were determined by delivering fast voltage ramps before and during the application of 2-methylthio ATP (300 microM). In the presence of extra- (1 mM) and intracellular (150 mM) Cs+, the 2-methylthio ATP-evoked current crossed the zero current level near 0 mV. When both Cs+ (1 mm) and 4-aminopyridine (1 mM) were present in the bath medium, the intersection of the 2-methylthio ATP current with the zero current level was near - 75 mV.6. 2-Methylthio ATP (1-1I000 MicroM) induced the same inward current both in proliferating and nonproliferating microglia. However, the depolarizing response to 2-methylthio ATP (300 MicroM) was larger and longer-lasting in the proliferating cells. When the free Ca2+ concentration in the pipettes was increased from the standard 0.01 to 1 MicroM, the amplitude and duration of this depolarization was increased in non-proliferating cells. 4-Aminopyridine (1 mM) enhanced the duration, but not the amplitude of responses.7. ATP and its structural analogues stimulate microglial purinoceptors of the P2Y-type. This leads to the opening of non-selective cationic channels and potassium channels. Depending on the resting membrane potential, depolarization or hyperpolarization prevails. Although the inward current produced by 2-methylthio ATP is of similar amplitude in proliferating and non-proliferating microglia, the resulting depolarization is smaller in the latter cell type because of the presence of voltage-sensitive, outwardly rectifying potassium channels.

Adenosine Triphosphate↗
PubMed1994

Characterization and transduction mechanisms of purinoceptors in activated rat microglia.

1. Purinoceptor agonist-induced currents in untreated (proliferating) and lipopolysaccharide- (LPS; 100 ng ml-1) treated (non-proliferating) rat microglial cells were recorded by the whole-cell patch-clamp technique. 2. In non-proliferating microglia, adenosine (0.01-100 microM), 2-methylthio ATP (3-3000 nM), ATP (0.1-1000 microM), and ATP-gamma-S (1-10 microM), but not alpha,beta-methylene ATP (alpha,beta-MeATP; 100 microM) produced a slow outward current at a holding potential of 0 mV. When K+ was replaced in the pipette solution by an equimolar concentration of Cs+ (150 mM), the 2-methylthio ATP- (300 nM) induced outward current disappeared. The effect of 2-methylthio ATP (300 nM) did not depend on the presence of extracellular Mg2+ (1 mM). The outward current response to 2-methylthio ATP (300 nM) was larger in proliferating than in non-proliferating microglia. 3. ATP (1-1000 microM) evoked a fast inward current at a holding potential of -70 mV in nonproliferating microglia, while adenosine (100-1000 microM) was inactive. When the effects of ATP were compared at 0 and -70 mV, it became evident that ATP is much more potent in evoking the outward current. 4. The 2-methylthio ATP- (300 nM) induced outward current was blocked by suramin (300 microM), but not by 8-(p-sulphophenyl)-theophylline (100 microM), while the adenosine- (1 microM) induced outward current had the reverse sensitivity to these antagonists. 5. The 2-methylthio ATP- (300 nM) induced outward current was inhibited by inclusion of GDP-beta-S(200 microM) into the pipette solution or by preincubation of microglial cells with pertussis toxin(50 ng ml-1) for 12 h. The 2-methylthio ATP- (300 microM) induced inward current was not changed by intracellular GDP-beta-S (200 microM). The outward current response to adenosine (1 microM) was also abolished after pretreatment with pertussis toxin (50 ng ml-1).6. Rat microglia possess both ATP-sensitive P2y- and adenosine-sensitive P1-purinoceptors. The ATP evoked inward current is mediated by P2y-purinoceptors, while the ATP- and adenosine-evoked outward currents are mediated by P2y- and P1-purinoceptors, respectively. The transduction mechanisms of the outward, but not the inward current activation involve a pertussis toxin-sensitive G protein.

Adenosine Triphosphate↗