Search results for "Reuptake"
showing 10 items of 96 documents
Synthesis and pharmacology of 6-substituted benztropines: discovery of novel dopamine uptake inhibitors possessing low binding affinity to the dopami…
2005
A series of 6alpha- and 6beta-substituted benztropines were synthesized. A marked enantioselectivity was observed for the 6beta-methoxylated benztropines, the (1R)-isomers being more potent than the corresponding (1S) compounds. The racemic 6alpha-methoxy-3-(4',4' '-difluorodiphenylmethoxy)tropane (5 g) was the most potent compound. It has been found that modifications at the 6-position of benztropine might reduce the DAT binding affinity, maintaining otherwise a significant dopamine uptake inhibitory activity. A reinvestigation of the absolute configuration of 6beta-methoxytropinone proved the 6R configuration for the (+)-enantiomer.
Meta-Analysis, Ideals of Objectivity, and the Reliability of Medical Knowledge
2015
This paper focuses on the ideals of scientific objectivity as they emerge in discussions concerning meta-analyses and medical research. Stegenga (2011) has argued that meta-analyses fail to be objective because conducting them involves making judgments. I show that his reasoning is based on the so-called procedural ideal of objectivity, which can be questioned: this ideal is unattainable and does not capture some of the problematic issues of medical research. By introducing a case in research on selective serotonin reuptake inhibitors, I demonstrate why the so-called social view on objectivity succeeds better in accommodating 1) the way in which scientific research necessarily involves judg…
Antidepressant drugs and memory: Insights from animal studies
2007
This is a selective review of the literature concerning the effects of antidepressant drugs on animal memory, which was performed with the aid of the PubMed database. Monoamine oxidase inhibitors tend to either have no effect on memory or result in its improvement. Studies with cyclic antidepressants have reported no effect or, more often, memory impairments. Pre-training administration of selective serotonin reuptake inhibitors (SSRIs) has been shown to have either no effect on memory or undermine it (with some isolated exceptions, in which improvements have been recorded), while post-training administration of SSRIs has been demonstrated to improve memory or have no effect. A small group …
Subchronic vortioxetine treatment -but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex.
2017
Abstract Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT 3 -R, 5-HT 7 -R and 5-HT 1D -R antagonist, 5-HT 1B -R partial agonist, 5-HT 1A -R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p -chlorophenylalanine -pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of …
Conventional and spectral power analysis of all-night sleep EEG after subchronic treatment with paroxetine in healthy male volunteers.
1998
Paroxetine is a selective and potent serotonin reuptake inhibitor with reported antidepressant properties. Since changes in the regular sleeping pattern were described as side effects under treatment with paroxetine, the impact of the drug on the sleep architecture is of major interest. The present study addressed the question of subchronic effects of paroxetine medication (30 mg/day) in eight healthy male volunteers in a double blind, placebo-controlled crossover-design. Conventional sleep EEG parameters and additionally computed spectral power analysis based on FFT of 20-s time epochs in the delta, theta, alpha, beta and gamma frequency range for different sleep stages after 4 weeks of tr…
The diagnosis of and treatment recommendations for anxiety disorders.
2014
Anxiety disorders (panic disorder/agoraphobia, generalized anxiety disorder, social phobia, and specific phobias) are the most common mental illnesses. For example, the 12-month prevalence of panic disorder/agoraphobia is 6%.This guideline is based on controlled trials of psychotherapy and pharmacotherapy, retrieved by a systematic search for original articles that were published up to 1 July 2013. Experts from 20 specialty societies and other organizations evaluated the evidence for each treatment option from all available randomized clinical trials and from a synthesis of the recommendations of already existing international and German guidelines.403 randomized controlled trials were eval…
Severe Tremor After Cotrimoxazole-Induced Elevation of Venlafaxine Serum Concentrations in a Patient With Major Depressive Disorder
2013
: We describe a female patient who was an extensive metabolizer of cytochrome P450 isoenzyme (CYP) 2D6 and an intermediate metabolizer of CYP2C19 (genotype: CYP2C19 *1/*2). She exhibited high serum concentrations of venlafaxine and O-desmethylvenlafaxine and developed severe tremor after comedication with cotrimoxazole (sulfamethazole/trimethoprim). Venlafaxine is mainly metabolized by O- and N-demethylation. O-demethylation is catalyzed by the highly polymorphic CYP2D6 and N-demethylation by several enzymes, CYP2C19, CYP2C9, and CYP3A4. The observed overall pharmacokinetic effect was most probably the result of decreased N-demethylation of venlafaxine by (1) reduced expression of CYP2C19 d…
Nicotine receptors do not modulate the 3H-noradrenaline release from the isolated rat heart evoked by sympathetic nerve stimulation.
1982
Isolated rat hearts with the right sympathetic nerves attached were perfused at a constant flow rate of 7 ml/min with Tyrode's solution. (-)-3H-Noradrenaline (final concentration 10–13.9 nM) was infused for 10 min to label the noradrenaline stores. After wash-out the sympathetic nerves were stimulated electrically (3 Hz, 180 impulses, 1 ms, 20–30 mA) three times (S1–S3) at intervals of 15 min. 3H-Noradrenaline and its metabolites were determined by liquid scintillation counting according to Graefe et al. (1973). Both, nicotine 50 μM and p-aminophenethyltrimethylammonium (PAPETA) 30 μM, enhanced the 3H-noradrenaline overflow in the absence of nerve stimulation. The effect of PAPETA was bipha…
Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake
2017
The extracellular effects of the endocannabinoids anandamide and 2-arachidonoyl glycerol are terminated by enzymatic hydrolysis after crossing cellular membranes by facilitated diffusion. The lack of potent and selective inhibitors for endocannabinoid transport has prevented the molecular characterization of this process, thus hindering its biochemical investigation and pharmacological exploitation. Here, we report the design, chemical synthesis, and biological profiling of natural product-derived N-substituted 2,4-dodecadienamides as a selective endocannabinoid uptake inhibitor. The highly potent (IC50 = 10 nM) inhibitor N-(3,4-dimethoxyphenyl)ethyl amide (WOBE437) exerted pronounced canna…
Effects of co-administration of amitriptyline and fluoxetine on inhibitory avoidance in mice
2010
We have previously observed that, while the impairing effects of amitriptyline on inhibitory avoidance in mice are consistently observed, those of acute fluoxetine are negligible. Two experiments were designed to investigate whether a regular dose of fluoxetine potentiates the effect of a low dose of amitriptyline that is ineffective when administered alone. Male and female CD1 mice were administered i.p. 30 min before training, as follows. In the first experiment, they were injected with saline, one of three doses of amitriptyline (2.5, 5, 10 mg/kg), one dose of fluoxetine (15 mg/kg), or a combination of amitriptyline (2.5 mg/kg) and fluoxetine (15 mg/kg). In the second experiment, the mic…