BACKGROUND: Antipsychotics are indispensable in the treatment of severe mental illneses, however adverse metabolic effects including diabetes, weight gain, dyslipidemia, and related cardiovascular morbidity are common, and current pharmacological strategies for their management are unsatisfactory. Glucagon-like 1 peptide receptor agonists (GLP-1 RAs) are approved for the treatment of type 2 diabetes and obesity hold promise for the management of antipsychotic-associated adverse metabolic effects. METHODS: To characterize the molecular effects and identify biomarkers for GLP-1 RA preventive treatment, Sprague-Dawley female rats were treated with long-acting formulations of the antipsychotic olanzapine and the GLP-1 RA dulaglutide for 8 days. A pair-feeding protocol evaluated the combined effects of dulaglutide and food restriction on an olanzapine-induced metabolic phenotype. Body weight and food consumption were recorded. Biochemical analysis included a lipid profile, a spectrum of gastrointestinal and adipose tissue-derived hormones, and fibroblast growth factor 21 serum levels. RESULTS: Olanzapine induced hyperphagia, weight gain, increased serum triglycerides and HDL cholesterol. Food restriction affected the OLA-induced phenotype but not serum markers. Dulaglutide led to a modest decrease in food intake, with no effect on weight gain, and did not reverse the OLA-induced changes in serum lipid parameters. Concomitant dulaglutide and food restriction resulted in weight loss, decreased feed efficiency, and lower total and HDL cholesterol. CONCLUSIONS: A combined strategy of dulaglutide and food restriction manifested a massive synergistic benefit. GLP-1RAs represent a promising strategy and deserve thorough future research. Our findings underline the potential importance of lifestyle intervention in addition to GLP-1 RA treatment.

• Klíčová slova
• Antipsychotic, GLP-1 receptor agonist, Olanzapine, metabolic adverse effects, Schizophrenia,
• MeSH
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• antipsychotika farmakologie   škodlivé účinky   MeSH
• benzodiazepiny farmakologie   škodlivé účinky   MeSH
• glukagonu podobné peptidy * analogy a deriváty   farmakologie   MeSH
• hmotnostní přírůstek účinky léků   MeSH
• imunoglobuliny - Fc fragmenty * farmakologie   MeSH
• kalorická restrikce metody   MeSH
• krysa rodu Rattus MeSH
• modely nemocí na zvířatech MeSH
• olanzapin * farmakologie   škodlivé účinky   MeSH
• potkani Sprague-Dawley * MeSH
• přijímání potravy účinky léků   MeSH
• receptor pro glukagonu podobný peptid 1 metabolismus   MeSH
• rekombinantní fúzní proteiny * farmakologie   MeSH
• tělesná hmotnost účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• antipsychotika MeSH
• benzodiazepiny MeSH
• dulaglutide MeSH Prohlížeč
• glukagonu podobné peptidy * MeSH
• imunoglobuliny - Fc fragmenty * MeSH
• olanzapin * MeSH
• receptor pro glukagonu podobný peptid 1 MeSH
• rekombinantní fúzní proteiny * MeSH

OBJECTIVE: To obtain information on the transport of carbamazepine and its active metabolite carbamazepine-epoxide from mother to colostrum and breastfed newborns. METHODS: In this cohort study, carbamazepine and carbamazepine-epoxide concentrations in maternal serum (162 women), milk (i.e., colostrum) and breastfed newborn serum were analysed between the 1st and 5th days after delivery from November 1990 to February 2021. The measured concentrations were compared with the delivery and mature milk periods. The effect of the combination with both enzyme-inducing antiseizure medication and valproic acid was also evaluated. RESULTS: Carbamazepine concentrations varied from 1.0 to 11.2 mg/L (epoxide 0.3-4.4 mg/L) in maternal serum, from 0.5 to 6.8 mg/L (epoxide 0.3-2.4 mg/L) in milk and from 0.5 to 4.7 mg/L (epoxide 0.3-1.7 mg/L) in newborn serum. The median milk/maternal serum concentration ratio of carbamazepine was 0.45 (epoxide 0.71), the median newborn/maternal serum concentration ratio of carbamazepine was 0.20 (epoxide 0.41), and the median newborn serum/milk concentration ratio of carbamazepine was 0.38 (epoxide 0.50). A highly significant correlation was found between the milk and maternal serum concentrations of both carbamazepine and carbamazepine-epoxide and between the milk and newborn serum concentrations of carbamazepine. CONCLUSIONS: In the serum of breastfed newborns, only one concentration of carbamazepine reached the reference range used for the general epileptic population, and more than half was below the lower limit of quantification. Routine monitoring of serum carbamazepine concentrations is not required in breastfed newborns. However, observation of newborns is desirable, and if signs of potential adverse reactions are noted, the serum concentrations in newborns should be measured.

• Klíčová slova
• Carbamazepine, Carbamazepine-epoxide, Colostrum, Concentrations, Therapeutic drug monitoring,
• MeSH
• antikonvulziva terapeutické užití   MeSH
• benzodiazepiny farmakologie   MeSH
• epoxidové sloučeniny farmakologie   MeSH
• karbamazepin MeSH
• kohortové studie MeSH
• kojení * MeSH
• kolostrum metabolismus   MeSH
• lidé MeSH
• mateřské mléko metabolismus   MeSH
• matky * MeSH
• novorozenec MeSH
• těhotenství MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antikonvulziva MeSH
• benzodiazepiny MeSH
• epoxidové sloučeniny MeSH
• karbamazepin MeSH

Benzodiazepines (BZDs) are widely used in patients of all ages. Unlike adults, neonatal animals treated with BZDs exhibit a variety of behavioral deficits later in life; however, the mechanisms underlying these deficits are poorly understood. This study aims to examine whether administration of clonazepam (CZP; 1 mg/kg/day) in 7-11-day-old rats affects Gama aminobutyric acid (GABA)ergic receptors in both the short and long terms. Using RT-PCR and quantitative autoradiography, we examined the expression of the selected GABAA receptor subunits (α1, α2, α4, γ2, and δ) and the GABAB B2 subunit, and GABAA, benzodiazepine, and GABAB receptor binding 48 h, 1 week, and 2 months after treatment discontinuation. Within one week after CZP cessation, the expression of the α2 subunit was upregulated, whereas that of the δ subunit was downregulated in both the hippocampus and cortex. In the hippocampus, the α4 subunit was downregulated after the 2-month interval. Changes in receptor binding were highly dependent on the receptor type, the interval after treatment cessation, and the brain structure. GABAA receptor binding was increased in almost all of the brain structures after the 48-h interval. BZD-binding was decreased in many brain structures involved in the neuronal networks associated with emotional behavior, anxiety, and cognitive functions after the 2-month interval. Binding of the GABAB receptors changed depending on the interval and brain structure. Overall, the described changes may affect both synaptic development and functioning and may potentially cause behavioral impairment.

• Klíčová slova
• GABAA/BZD receptor binding, GABAB receptor binding, clonazepam, neonatal rat, subunit mRNA expression,
• MeSH
• benzodiazepiny farmakologie   MeSH
• GABA metabolismus   MeSH
• hipokampus účinky léků   metabolismus   MeSH
• klonazepam farmakologie   MeSH
• krysa rodu Rattus MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• mozek účinky léků   metabolismus   MeSH
• novorozená zvířata MeSH
• potkani inbrední WF MeSH
• receptory GABA-A metabolismus   MeSH
• receptory GABA-B metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzodiazepiny MeSH
• GABA MeSH
• klonazepam MeSH
• receptory GABA-A MeSH
• receptory GABA-B MeSH

Antitumor pyrrolobenzodiazepines (PBDs), lincosamide antibiotics, quorum-sensing molecule hormaomycin, and antimicrobial griselimycin are structurally and functionally diverse groups of actinobacterial metabolites. The common feature of these compounds is the incorporation of l-tyrosine- or l-leucine-derived 4-alkyl-l-proline derivatives (APDs) in their structures. Here, we report that the last reaction in the biosynthetic pathway of APDs, catalyzed by F420H2-dependent Apd6 reductases, contributes to the structural diversity of APD precursors. Specifically, the heterologous overproduction of six Apd6 enzymes demonstrated that Apd6 from the biosynthesis of PBDs and hormaomycin can reduce only an endocyclic imine double bond, whereas Apd6 LmbY and partially GriH from the biosyntheses of lincomycin and griselimycin, respectively, also reduce the more inert exocyclic double bond of the same 4-substituted Δ1-pyrroline-2-carboxylic acid substrate, making LmbY and GriH unusual, if not unique, among reductases. Furthermore, the differences in the reaction specificity of the Apd6 reductases determine the formation of the fully saturated APD moiety of lincomycin versus the unsaturated APD moiety of PBDs, providing molecules with optimal shapes to bind their distinct biological targets. Moreover, the Apd6 reductases establish the first F420H2-dependent enzymes from the luciferase-like hydride transferase protein superfamily in the biosynthesis of bioactive molecules. Finally, our bioinformatics analysis demonstrates that Apd6 and their homologues, widely distributed within several bacterial phyla, play a role in the formation of novel yet unknown natural products with incorporated l-proline-like precursors and likely in the microbial central metabolism.

• MeSH
• benzodiazepiny chemie   metabolismus   farmakologie   MeSH
• cyklické peptidy biosyntéza   chemie   farmakologie   MeSH
• depsipeptidy biosyntéza   chemie   farmakologie   MeSH
• katalýza MeSH
• linkomycin biosyntéza   chemie   farmakologie   MeSH
• molekulární modely MeSH
• oxidoreduktasy chemie   metabolismus   MeSH
• prolin analogy a deriváty   metabolismus   MeSH
• pyrroly chemie   metabolismus   farmakologie   MeSH
• riboflavin analogy a deriváty   chemie   metabolismus   MeSH
• substrátová specifita MeSH
• tyrosin analogy a deriváty   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzodiazepiny MeSH
• coenzyme F420 MeSH Prohlížeč
• cyklické peptidy MeSH
• depsipeptidy MeSH
• F420H2 dehydrogenase MeSH Prohlížeč
• griselimycin MeSH Prohlížeč
• hormaomycin MeSH Prohlížeč
• linkomycin MeSH
• oxidoreduktasy MeSH
• prolin MeSH
• pyrrolo(2,1-c)(1,4)benzodiazepine MeSH Prohlížeč
• pyrroly MeSH
• riboflavin MeSH
• tyrosin MeSH

Covering: up to 2017This review covers the biosynthetic and evolutionary aspects of lincosamide antibiotics, antitumour pyrrolobenzodiazepines (PBDs) and the quorum-sensing molecule hormaomycin. These structurally and functionally diverse groups of complex natural products all incorporate rarely occurring 4-alkyl-l-proline derivatives (APDs) biosynthesized from l-tyrosine through an unusual specialized pathway catalysed by a common set of six proteins named Apd1-Apd6. We give an overview of APD formation, which involves unusual enzyme activities, and its incorporation, which is based either on nonribosomal peptide synthetase (PBDs, hormaomycin) or a unique hybrid ergothioneine-dependent condensation system followed by mycothiol-dependent sulphur atom incorporation (lincosamides). Furthermore, within the public databases, we identified 36 novel unannotated biosynthetic gene clusters that putatively encode the biosynthesis of APD compounds. Their products presumably include novel PBDs, but also novel classes of APD compounds, indicating an unprecedented potential for the diversity enhancement of these functionally versatile complex metabolites. In addition, phylogenetic analysis of known and novel gene clusters for the biosynthesis of APD compounds allowed us to infer novel evolutionary hypotheses: Apd3 methyltransferase originates from a duplication event in a hormaomycin biosynthetic gene cluster ancestor, while putative Apd5 isomerase is evolutionarily linked to PhzF protein from the biosynthesis of phenazines. Lastly, we summarize the achievements in preparing hybrid APD compounds by directing their biosynthesis, and we propose that the number of nature-like APD compounds could by multiplied by replacing l-proline residues in various groups of complex metabolites with APD, i.e. by imitating the natural process that occurs with lincosamides and PBDs, in which the replacement of l-proline for APD has proved to be an evolutionary successful concept.

• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• benzodiazepiny chemie   farmakologie   MeSH
• biologické přípravky chemie   metabolismus   farmakologie   MeSH
• cystein metabolismus   MeSH
• depsipeptidy chemie   metabolismus   farmakologie   MeSH
• ergothionein metabolismus   MeSH
• glykopeptidy metabolismus   MeSH
• inositol metabolismus   MeSH
• lidé MeSH
• linkomycin chemie   farmakologie   MeSH
• linkosamidy biosyntéza   farmakologie   MeSH
• molekulární evoluce * MeSH
• molekulární struktura MeSH
• protinádorové látky chemie   metabolismus   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH
• benzodiazepiny MeSH
• biologické přípravky MeSH
• cystein MeSH
• depsipeptidy MeSH
• ergothionein MeSH
• glykopeptidy MeSH
• hormaomycin MeSH Prohlížeč
• inositol MeSH
• linkomycin MeSH
• linkosamidy MeSH
• mycothiol MeSH Prohlížeč
• protinádorové látky MeSH

OBJECTIVE: Mitochondrial dysfunctions, impaired bioenergetics and dysfunction of neurotrophins are included in many neurodegenerative and psychiatric diseases. We investigated in vitro effects of pharmacologically different antidepressants and mood stabilizers on mitochondrial enzymes to discover, which mitochondrial functions could be involved in pathophysiology of mood disorders. METHODS: In vitro effects of eight pharmacologically different antidepressants (desipramine, amitriptyline, imipramine, citalopram, venlafaxine, mirtazapine, tianeptine, and moclobemide) and three mood stabilizers (lithium, valproate, and olanzapine) on the activities of mitochondrial enzymes (citrate synthase and enzymes in electron transport chain, i.e. complexes I, II, IV) were measured in crude mitochondrial fraction isolated from pig brain. RESULTS: Most of the antidepressants and mood stabilizers inhibited the activities of respiratory electron transport chain complexes, complexes I and IV were the most affected. Statistically significant decrease of the complex I activity was caused by desipramine, amitriptyline, imipramine, citalopram, mirtazapine, valproate and olanzapine. Complex II was significantly inhibited only by amitriptyline, imipramine, citalopram and venlafaxine. Complex IV was significantly inhibited by all tested drugs except for citalopram and moclobemide. Unchanged or slightly increased citrate synthase activity was observed; significant activation of the enzyme was observed after citalopram, tianeptine and olanzapine. CONCLUSIONS: Our results indicate that antidepressants may act generally as inhibitors of complex I and complex IV of the electron transport chain. These mitochondrial enzymes are suggested as proper candidates in searching of new biological markers of mood disorders, targets of new antidepressants or predictors of response to pharmacotherapy.

• MeSH
• antidepresiva farmakologie   MeSH
• antipsychotika farmakologie   MeSH
• benzodiazepiny farmakologie   MeSH
• citrátsynthasa metabolismus   MeSH
• kyselina valproová farmakologie   MeSH
• mitochondrie účinky léků   MeSH
• mozková kůra účinky léků   metabolismus   MeSH
• olanzapin MeSH
• prasata MeSH
• respirační komplex I metabolismus   MeSH
• respirační komplex III metabolismus   MeSH
• respirační komplex IV metabolismus   MeSH
• sloučeniny lithia farmakologie   MeSH
• techniky in vitro MeSH
• transport elektronů účinky léků   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antidepresiva MeSH
• antipsychotika MeSH
• benzodiazepiny MeSH
• citrátsynthasa MeSH
• kyselina valproová MeSH
• olanzapin MeSH
• respirační komplex I MeSH
• respirační komplex III MeSH
• respirační komplex IV MeSH
• sloučeniny lithia MeSH

OBJECTIVE: Monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters, has an important role in the brain development and function, and MAO inhibitors have a range of potential therapeutic uses. We investigated systematically in vitro effects of pharmacologically different antidepressants and mood stabilizers on MAO activity. METHODS: Effects of drugs on the activity of MAO were measured in crude mitochondrial fraction isolated from cortex of pig brain, when radiolabeled serotonin (for MAO-A) or phenylethylamine (for MAO-B) was used as substrate. The several antidepressants and mood stabilizers were compared with effects of well known MAO inhibitors such as moclobemide, iproniazid, pargyline, and clorgyline. RESULTS: In general, the effect of tested drugs was found to be inhibitory. The half maximal inhibitory concentration, parameters of enzyme kinetic, and mechanism of inhibition were determined. MAO-A was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > desipramine > amitriptyline > imipramine > citalopram > venlafaxine > reboxetine > olanzapine > mirtazapine > tianeptine > moclobemide, cocaine >> lithium, valproate. MAO-B was inhibited by the following drugs: pargyline > clorgyline > iproniazid > fluoxetine > venlafaxine > amitriptyline > olanzapine > citalopram > desipramine > reboxetine > imipramine > tianeptine > mirtazapine, cocaine >> moclobemide, lithium, valproate. The mechanism of inhibition of MAOs by several antidepressants was found various. CONCLUSIONS: It was concluded that MAO activity is acutely affected by pharmacologically different antidepressants at relatively high drug concentrations; this effect is inhibitory. There are differences both in inhibitory potency and in mechanism of inhibition between both several drugs and the two MAO isoforms. While MAO inhibition is not primary biochemical effect related to their therapeutic action, it can be supposed that decrease of MAO activity may be concerned in some effects of these drugs on serotonergic, noradrenergic, and dopaminergic neurotransmission.

• MeSH
• afekt účinky léků   MeSH
• amitriptylin farmakologie   MeSH
• antidepresiva farmakologie   MeSH
• antimanika farmakologie   MeSH
• benzodiazepiny farmakologie   MeSH
• citalopram farmakologie   MeSH
• cyklohexanoly farmakologie   MeSH
• desipramin farmakologie   MeSH
• fluoxetin farmakologie   MeSH
• imipramin farmakologie   MeSH
• inhibitory MAO farmakologie   MeSH
• iproniazid farmakologie   MeSH
• klorgylin farmakologie   MeSH
• kokain farmakologie   MeSH
• kyselina valproová farmakologie   MeSH
• lithium farmakologie   MeSH
• mianserin analogy a deriváty   farmakologie   MeSH
• mirtazapin MeSH
• mitochondrie účinky léků   enzymologie   MeSH
• moklobemid farmakologie   MeSH
• monoaminoxidasa účinky léků   metabolismus   MeSH
• morfoliny farmakologie   MeSH
• mozková kůra cytologie   MeSH
• olanzapin MeSH
• pargylin farmakologie   MeSH
• prasata MeSH
• reboxetin MeSH
• techniky in vitro MeSH
• thiazepiny farmakologie   MeSH
• venlafaxin hydrochlorid MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amitriptylin MeSH
• antidepresiva MeSH
• antimanika MeSH
• benzodiazepiny MeSH
• citalopram MeSH
• cyklohexanoly MeSH
• desipramin MeSH
• fluoxetin MeSH
• imipramin MeSH
• inhibitory MAO MeSH
• iproniazid MeSH
• klorgylin MeSH
• kokain MeSH
• kyselina valproová MeSH
• lithium MeSH
• mianserin MeSH
• mirtazapin MeSH
• moklobemid MeSH
• monoaminoxidasa MeSH
• morfoliny MeSH
• olanzapin MeSH
• pargylin MeSH
• reboxetin MeSH
• thiazepiny MeSH
• tianeptine MeSH Prohlížeč
• venlafaxin hydrochlorid MeSH

The aim of our study was to detect changes in the distribution of electrical brain activity in schizophrenic patients who were antipsychotic naive and those who received treatment with clozapine, olanzapine or risperidone. We included 41 subjects with schizophrenia (antipsychotic naive = 11; clozapine = 8; olanzapine = 10; risperidone = 12) and 20 healthy controls. Low-resolution brain electromagnetic tomography was computed from 19-channel electroencephalography for the frequency bands delta, theta, alpha-1, alpha-2, beta-1, beta-2 and beta-3. We compared antipsychotic-naive subjects with healthy controls and medicated patients. (1) Comparing antipsychotic-naive subjects and controls we found a general increase in the slow delta and theta frequencies over the fronto-temporo-occipital cortex, particularly in the temporolimbic structures, an increase in alpha-1 and alpha-2 in the temporal cortex and an increase in beta-1 and beta-2 in the temporo-occipital and posterior limbic structures. (2) Comparing patients who received clozapine and those who were antipsychotic naive, we found an increase in delta and theta frequencies in the anterior cingulate and medial frontal cortex, and a decrease in alpha-1 and beta-2 in the occipital structures. (3) Comparing patients taking olanzapine with those who were antipsychotic naive, there was an increase in theta frequencies in the anterior cingulum, a decrease in alpha-1, beta-2 and beta-3 in the occipital cortex and posterior limbic structures, and a decrease in beta-3 in the frontotemporal cortex and anterior cingulum. (4) In patients taking risperidone, we found no significant changes from those who were antipsychotic naive. Our results in antipsychotic-naive patients are in agreement with existing functional findings. Changes in those taking clozapine and olanzapine versus those who were antipsychotic naive suggest a compensatory mechanism in the neurobiological substrate for schizophrenia. The lack of difference in risperidone patients versus antipsychotic-naive subjects may relate to risperidone's different pharmacodynamic mechanism.

• MeSH
• antipsychotika farmakologie   terapeutické užití   MeSH
• benzodiazepiny farmakologie   terapeutické užití   MeSH
• dospělí MeSH
• elektroencefalografie účinky léků   přístrojové vybavení   metody   MeSH
• klozapin farmakologie   terapeutické užití   MeSH
• lidé MeSH
• mapování mozku přístrojové vybavení   metody   MeSH
• mladý dospělý MeSH
• mozek účinky léků   patologie   patofyziologie   MeSH
• olanzapin MeSH
• počítačové zpracování signálu MeSH
• referenční hodnoty MeSH
• risperidon farmakologie   terapeutické užití   MeSH
• schizofrenie diagnóza   farmakoterapie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antipsychotika MeSH
• benzodiazepiny MeSH
• klozapin MeSH
• olanzapin MeSH
• risperidon MeSH

Dizocilpine (MK-801; 0.3 mg/kg i.p.)-induced disruption in prepulse inhibition of the acoustic startle response (PPI) can be preferentially restored by "atypical" antipsychotics. In contrast, some findings indicate that not all of the "atypical" antipsychotics, such as clozapine and risperidone, are effective in restoring the NMDA antagonist-induced deficits in PPI. In our study, we evaluated the effect of four different "atypical" antipsychotic drugs on deficits in PPI induced by MK-801. Zotepine and risperidone have high affinities to D2-like and 5-HT2A receptors, while clozapine and olanzapine have multipharmacological profiles with the highest affinities to serotonin 5-HT1A,2A/2C receptors and muscarinic receptors. Results have shown that MK-801 disrupted PPI and increased the ASR in rats. Our results showed no effect of zotepine (1 and 2 mg/kg) and risperidone (0.1 and 1 mg/kg) on disrupted PPI by MK-801. Administration of clozapine (5 and 10 mg/kg) and olanzapine (2.5 and 5 mg/kg) restored the deficits in PPI induced by MK-801. Additionally, we found a decrease of approximately 46% in PPI after administration of clozapine (5 mg/kg) and olanzapine (2.5 and 5 mg/kg) without MK-801 treatment. In summary, the four "atypical" antipsychotics had different efficacies to restore the disrupted PPI by MK-801. Only clozapine and olanzapin restored the MK-801-induced deficits in PPI.

• MeSH
• akustická stimulace MeSH
• antagonisté excitačních aminokyselin farmakologie   MeSH
• antipsychotika farmakologie   MeSH
• benzodiazepiny farmakologie   MeSH
• dibenzothiepiny farmakologie   MeSH
• dizocilpinmaleát antagonisté a inhibitory   farmakologie   MeSH
• klozapin farmakologie   MeSH
• krysa rodu Rattus MeSH
• olanzapin MeSH
• potkani Wistar MeSH
• receptor serotoninový 5-HT2A účinky léků   MeSH
• receptory dopaminu D2 agonisté   MeSH
• receptory muskarinové účinky léků   MeSH
• risperidon farmakologie   MeSH
• úleková reakce účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antagonisté excitačních aminokyselin MeSH
• antipsychotika MeSH
• benzodiazepiny MeSH
• dibenzothiepiny MeSH
• dizocilpinmaleát MeSH
• klozapin MeSH
• olanzapin MeSH
• receptor serotoninový 5-HT2A MeSH
• receptory dopaminu D2 MeSH
• receptory muskarinové MeSH
• risperidon MeSH
• zotepine MeSH Prohlížeč

The dorsal horn of the spinal cord contains many transmitters and receptors involving in pain transmission and modulation. Monoamines and gamma-aminobutyric acid (GABA) play a key role in the modulation at level of dorsal horn (DH) of the spinal cord, the site of primary processing of afferent nociceptive information. Agents that enhance the action of GABA at the GABAA receptors can produce antinociception. For example intrathecal administration of benzodiazepines increases pain threshold in various models of pain. There is also substantial evidence for robust antinociceptive properties of spinal administration of clonidine and other alpha 2-agonists.

• MeSH
• agonisté adrenergních alfa-receptorů farmakologie   MeSH
• alfa-2-adrenergní receptory - agonisté MeSH
• alfa-2-adrenergní receptory fyziologie   MeSH
• benzodiazepiny farmakologie   MeSH
• bolest patofyziologie   MeSH
• GABA fyziologie   MeSH
• lidé MeSH
• neurotransmiterové látky farmakologie   MeSH
• práh bolesti účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• agonisté adrenergních alfa-receptorů MeSH
• alfa-2-adrenergní receptory - agonisté MeSH
• alfa-2-adrenergní receptory MeSH
• benzodiazepiny MeSH
• GABA MeSH
• neurotransmiterové látky MeSH