Search results for "serotonin"

Influence of concomitant medications on the total clearance and the risk for supra-therapeutic plasma concentrations of Citalopram. A population-base…

2014

Introduction: The main objective of this study was to investigate the influence of the use of multiple medications and other risk factors on citalopram plasma concentrations. Methods: A retrospective cohort study with a naturalistic population of 957 patients for whom routine therapeutic drug monitoring (TDM) of citalopram had been requested between 2006 and 2013 was conducted. Results: Concomitant drugs inhibiting at least 2 different CYP subtypes involved in the metabolism of citalopram decreased statistically significantly the total clearance (Clt). Compared to younger patients over 64-year-old patients had on average a 4.5 times higher risk rate of supra-therapeutic plasma concentration…

Positron emission tomography in CNS drug discovery and drug monitoring.

2014

Molecular imaging methods such as positron emission tomography (PET) are increasingly involved in the development of new drugs. Using radioactive tracers as imaging probes, PET allows the determination of the pharmacokinetic and pharmacodynamic properties of a drug candidate, via recording target engagement, the pattern of distribution, and metabolism. Because of the noninvasive nature and quantitative end point obtainable by molecular imaging, it seems inherently suited for the examination of a pharmaceutical’s behavior in the brain. Molecular imaging, most especially PET, can therefore be a valuable tool in CNS drug research. In this Perspective, we present the basic principles of PET, th…

Structural effects and neurofunctional sequelae of developmental exposure to psychotherapeutic drugs: experimental and clinical aspects

2004

The advent of psychotherapeutic drugs has enabled management of mental illness and other neurological problems such as epilepsy in the general population, without requiring hospitalization. The success of these drugs in controlling symptoms has led to their widespread use in the vulnerable population of pregnant women as well, where the potential embryotoxicity of the drugs has to be weighed against the potential problems of the maternal neurological state. This review focuses on the developmental toxicity and neurotoxicity of five broad categories of widely available psychotherapeutic drugs: the neuroleptics, the antiepileptics, the antidepressants, the anxiolytics and mood stabilizers, an…

Assaying waterborne psychoactive drugs by the response to naturalistic predator cues in the stickleback (Gasterosteus aculeatus)

2020

Abstract Ecotoxicological effects of psychiatric drugs and drug metabolites released by the human population are of increasing environmental concern. In this study we evaluate behavioral responses to visual predator cues in wild caught three-spined stickleback (Gasterosteus aculeatus) after exposure to water-born citalopram, a widely prescribed selective serotonin reuptake inhibitor with antidepressant and anxiolytic effects. Fish were exposed to ecological relevant concentrations of citalopram (0.15 or 1.5 μg L−1) for 10 or 20 days. After drug exposure, individual fish were moved to a test arena where they were exposed to two naturalistic visual predator cues; a shadow from beneath, which …

Axons take a dive

2014

In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular-subventricular zone (V-SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the functio…

ROLE OF SEROTONIN1A/2A/2C RECEPTORS IN THE MODULATION OF NORMAL AND PATHOLOGICAL HIPPOCAMPAL EXCITABILITY

2015

Effects of the benzodiazepine receptor agonist midazolam and antagonist flumazenil on 5-hydroxytryptamine release from guinea-pig intestine in vitro

1990

Isolated segments of the guinea-pig small intestine and the guinea-pig stomach were vascularly perfused and the release of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid into the portal venous effluent determined by high pressure liquid chromatography with electrochemical detection. Test substances were applied intraarterially. The benzodiazepine receptor agonist, midazolam, concentration-dependently increased (by 58%, at 1 nmol/l) and decreased (by 32%, at 100 nmol/l) the release of 5-HT from small intestine preparations. Both effects were blocked by the benzodiazepine receptor antagonist flumazenil (10 nmol/l) The stimulatory effect of midazolam was also abolished in the presen…

P-Glycoprotein Influence on the Brain Uptake of a 5-HT2A Ligand: [18F]MH.MZ

2010

<i>Background/Aims:</i> The serotonergic system, especially the 5-HT<sub>2A</sub> receptor, is involved in various diseases and conditions. We have recently developed a new [<sup>18</sup>F]-5-HT<sub>2A</sub> receptor ligand using an analogue, MDL 100907, as a basis for molecular imaging with positron emission tomography. This tracer, [<sup>18</sup>F]MH.MZ, has been shown to be an adequate tool to visualize the 5-HT<sub>2A</sub> receptors in vivo. However, [<sup>18</sup>F]altanserin, similar in chemical structure, is a substrate of efflux transporters, such as P-glycoprotein (P-gp), of the blood-brain barrier…

SYNTHESIS AND IN VITRO AFFINITIES OF VARIOUS MDL 100907 DERIVATIVES AS POTENTIAL 18F-RADIOLIGANDS FOR 5-HT2A RECEPTOR IMAGING WITH PET

2008

Radiolabelled piperidine derivatives such as [(11)C]MDL 100907 and [(18)F]altanserin have played an important role in diagnosing malfunction in the serotonergic neurotransmission. A variety of novel piperidine MDL 100907 derivatives, possible to label with (18)F-fluorine, were synthesized to improve molecular imaging properties of [(11)C]MDL 100907. Their in vitro affinities to a broad spectrum of neuroreceptors and their lipophilicities were determined and compared to the clinically used reference compounds MDL 100907 and altanserin. The novel compounds MA-1 (53) and (R)-MH.MZ (56) show K(i)-values in the nanomolar range towards the 5-HT(2A) receptor and insignificant binding to other 5-HT…

Total synthesis and evaluation of [18F]MHMZ.

2007

Radiochemical labeling of MDL 105725 using the secondary labeling precursor 2-[(18)F]fluoroethyltosylate ([(18)F]FETos) was carried out in yields of approximately 90% synthesizing [(18)F]MHMZ in a specific activity of approximately 50MBq/nmol with a starting activity of approximately 3GBq. Overall radiochemical yield including [(18)F]FETos synthon synthesis, [(18)F]fluoroalkylation and preparing the injectable [(18)F]MHMZ solution was 42% within a synthesis time of approximately 100 min. The novel compound showed excellent specific binding to the 5-HT(2A) receptor (K(i)=9.0 nM) in vitro and promising in vivo characteristics.