• MeSH
• abúzus marihuany komplikace   patologie   psychologie   MeSH
• Cannabis chemie   MeSH
• centrální nervový systém účinky léků   MeSH
• finanční podpora výzkumu jako téma MeSH
• kanabinoidy farmakokinetika   farmakologie   MeSH
• kouření marihuany škodlivé účinky   MeSH
• lidé MeSH
• receptory kanabinoidní MeSH
• tetrahydrokanabinol terapeutické užití   MeSH
• Check Tag
• lidé MeSH

We investigated the kinetic parameters of serotonin (5-HT) uptake into platelets in a group of 26 drug-naive patients suffering from major depression before and after 3-7 weeks of treatment with citalopram. The degree of depression was rated using the Hamilton Depression Rating Scale (HDRS). The 5-HT uptake characteristics in untreated depressive patients were not significantly different from those of normal subjects. The apparent Michaelis constant (K(M)) was significantly increased, the apparent maximal velocity (V(max)) was not different from baseline, and the uptake efficiency (V(max)/K(M)) was significantly decreased after citalopram treatment. A significantly positive correlation between K(M) and V(max) was found in all groups. There was a significantly lower V(max) and V(max)/K(M) in the female compared with the male depressed patients before citalopram treatment; a hypothesis was supported that lowered 5-HT uptake may reflect a gender-linked vulnerability to a serotonin-related depression. A significant negative correlation between 5-HT uptake efficiency and the initial HDRS score suggests that platelet 5-HT uptake can be used as a marker of effective depressive disorder pharmacotherapy. The initial severity of depression was significantly negatively correlated with V(max), which supported a hypothesis that the initial severity of depressive disorder could be related to the lower V(max).

• MeSH
• citalopram farmakologie   terapeutické užití   MeSH
• depresivní porucha unipolární diagnóza   farmakoterapie   krev   MeSH
• dospělí MeSH
• fluoxetin farmakologie   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• serotonin metabolismus   MeSH
• sexuální faktory MeSH
• stupeň závažnosti nemoci MeSH
• trombocyty metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH

• MeSH
• agonisté kanabinoidních receptorů MeSH
• buněčná membrána MeSH
• finanční podpora výzkumu jako téma MeSH
• interakce mezi receptory a ligandy MeSH
• kyselina arachidonová MeSH
• lipidové dvojvrstvy MeSH
• membránové lipidy MeSH
• modulátory kanabinoidních receptorů biosyntéza   farmakokinetika   MeSH
• receptory kanabinoidní MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH

• Publikační typ
• abstrakt z konference MeSH

OBJECTIVE: The distribution of different antidepressants between plasma and red blood cells (RBCs) or between water and erythrocyte membranes (ghosts) has not been sufficiently compared so far. MATERIALS AND METHODS: Distribution of seven antidepressants (amitriptyline, nortriptyline, imipramine, desipramine, didesmethylimipramine, dothiepin, and citalopram) was measured in vitro in small volumes of blood or erythrocyte membrane suspension using radiolabeled drugs. Blood samples were taken from healthy subjects. RESULTS: The distribution of antidepressants between plasma and RBCs is strongly affected by temperature; however, it does not depend on the antidepressant concentration in the range of their therapeutic concentrations. The data analysis proved that the ratio of RBCs to plasma volume concentrations is the suitable parameter characterizing antidepressant distribution in whole blood. Significantly higher ratios of RBCs to plasma concentrations were found for demethylated metabolites of tricyclic antidepressants and in the case of citalopram. Citalopram showed the highest accumulation in intact RBCs and at the same time the lowest binding to isolated membranes. The binding of drugs to isolated erythrocyte membranes was much higher than in whole blood. CONCLUSION: The concentration ratio of antidepressant in RBCs and in plasma is sensitive not only to the binding properties of plasma proteins and cell membranes, but also to changes in drug molecule, both in aminopropyl chain and in aromatic rings. This ratio is to a large extent characteristic of a particular antidepressant.

• MeSH
• lidé MeSH
• Check Tag
• lidé MeSH

Cílem tohoto projektu je nalezení měřitelných biochemických a biofyzikálních parametrů citlivých na působení antidepresiv. Předpokládáme jejich využitelnost pro předpověď terapeutické odpovědi na psychofarmaka. Zaměříme se na studium vlastností buněčnýchsložek podílejících se na přenosu signálu (neurotransmiterových receptorů a membránových přenašečů, iontových kanálů, enzymů, systémů druhých poslů, membránového potenciálu, lipidové dvojvrstvy). V buňkách izolovaných z periferní lidské krve a na synaptosomech ze zvířecích mozků budou studovány účinky řady antidepresiv na membránové a nitrobuněčné procesy s využitím metod radionuklidových a fluorescenčních.; Contribution of our project consists in exploitation of modern methods to discover new pieces of knowledge in the field of molecular mechanisms of action of antidepressants.

• MeSH
• aktivní transport MeSH
• antidepresiva farmakokinetika   farmakologie   krev   MeSH
• biologický transport účinky léků   MeSH
• fluidita membrány MeSH
• fosfolipasy MeSH
• fyziologie buňky MeSH
• synaptozomy MeSH
• vápník MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biochemie
• farmacie a farmakologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

• MeSH
• aktivní transport účinky léků   MeSH
• antidepresiva farmakokinetika   farmakologie   terapeutické užití   MeSH
• depresivní poruchy farmakoterapie   MeSH
• fluidita membrány fyziologie   MeSH
• kanabinoidy farmakokinetika   farmakologie   terapeutické užití   MeSH
• membránové potenciály MeSH
• monoaminoxidasa účinky léků   MeSH
• neuroefektorové spoje MeSH
• neurotransmiterové látky farmakokinetika   farmakologie   fyziologie   krev   terapeutické užití   MeSH
• serotonin farmakokinetika   MeSH
• synaptické potenciály MeSH
• synaptozomy MeSH
• trombocyty účinky léků   MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• biochemie
• neurologie
• farmacie a farmakologie
• NLK Publikační typ
• studie

Progress in understanding the molecular mechanisms of cannabis action was made after discovery of cannabinoid receptors in the brain and the finding of endogenous metabolites with affinity to them. Activation of cannabinoid receptors on synaptic terminals results in regulation of ion channels, neurotransmitter release and synaptic plasticity. Neuromodulation of synapses by the cannabinoids is proving to have a wide range of functional effects, making them potential targets as medical preparations in a variety of illnesses, including some mental disorders and neurodegenerative illnesses. Cannabis contains a large amount of substances with affinity for the cannabinoid receptors. The endocannabinoids are a family of lipid neurotransmitters that engage the same membrane receptors targeted by tetrahydrocannabinol and that mediate retrograde signal from postsynaptic neurons to presynaptic ones. Discovery of endogenous cannabinoids and studies of the physiological functions of the cannabinoid system in the brain and body are producing a number of important findings about the role of membrane lipids and fatty acids in nerve signal transduction. Plant, endogenous and synthetic cannabinoids are using in these studies. The role of lipid membranes in the cannabinoid system follows from the fact that the source and supply of endogenous cannabinoids are derived from arachidonic acid, an important membrane constituent. The study of structure-activity relationships of molecules which influence the cannabinoid system in the brain and body is crucial in search of medical preparations with the therapeutic effects of the phytocannabinoids without the negative effects on cognitive function attributed to cannabis.

• MeSH
• Cannabis chemie   MeSH
• kanabinoidy farmakologie   chemie   MeSH
• léčivé rostliny chemie   MeSH
• lidé MeSH
• modulátory kanabinoidních receptorů metabolismus   MeSH
• receptory kanabinoidní metabolismus   účinky léků   MeSH
• signální transdukce fyziologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Serotonin is involved in many of the same processes affected by cannabinoids; therefore, we investigated in vitro and in vivo effects of these drugs on the function of serotonin transporter. The effect of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), endocannabinoid anandamide and synthetic cannabinoid receptor agonist WIN 55,212-2 on platelet serotonin uptake and membrane microviscosity was examined in 19 marijuana smokers and 20 controls. (1) Serotonin uptake was inhibited at higher doses of Delta(9)-THC (IC(50) = 139 micromol/l), anandamide (IC(50) = 201 micromol/l) or WIN 55,212-2 (IC(50) = 17.4 micromol/l); the inhibition was found non-competitive. Delta(9)-THC, anandamide and WIN 55,212-2 produced different effects on the membrane microviscosity. (2) Maximal velocity of platelet serotonin uptake was significantly increased in a group of chronic marijuana smokers suffering impairment of cognitive functions when compared with controls. Opposite effect of marijuana smoking on the serotonin uptake efficiency was observed in males beside females. In summary, this study provides evidence that (1) Activity of serotonin transporter is acutely affected by cannabinoids at relatively high drug concentrations; this effect is indirect and can be partially accounted for the changes in the membrane microviscosity. (2) Increase of maximal velocity of the serotonin uptake could be understood as adaptation change in the serotonergic system induced by chronic cannabis use. A hypothesis was supported that lowered serotonin uptake may reflect a gender-related differences in effects of psychoactive cannabinoids.

• MeSH
• benzoxaziny farmakologie   MeSH
• buněčná membrána účinky léků   MeSH
• dospělí MeSH
• financování organizované MeSH
• imipramin farmakologie   MeSH
• kanabinoidy farmakologie   MeSH
• kokain farmakologie   MeSH
• kouření marihuany krev   MeSH
• kyseliny arachidonové farmakologie   MeSH
• lidé MeSH
• membránové transportní proteiny pro serotonin účinky léků   MeSH
• morfoliny farmakologie   MeSH
• naftaleny farmakologie   MeSH
• pohlavní dimorfismus MeSH
• polynenasycené alkamidy farmakologie   MeSH
• techniky in vitro MeSH
• tetrahydrokanabinol farmakologie   MeSH
• trombocyty účinky léků   MeSH
• viskozita MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH