AMPA receptors (AMPARs) are responsible for fast excitatory neurotransmission, and their prolonged activation can result in the generation and spread of epileptic seizures. At early stages of postnatal development, the majority of AMPARs are permeable to both Na(+) and Ca(2+) ions. This permeability, which increases neuronal excitability, is due to the lack of the GluA2 subunit, encoded by the GRIA2A gene, and/or the presence of an unedited GluA2 subunit Q/R site (glutamine instead of arginine). Lithium chloride- and pilocarpine-induced status epilepticus (LiCl/Pilo-SE) in rodents represents a model of severe seizures that result in development of temporal lobe epilepsy (TLE). The aim of this study was to determine how LiCl/Pilo-SE induced early in life (at postnatal day 12; P12) alters normal expression of the GRIA2A gene and GluA2 protein. SE was interrupted by an injection of paraldehyde (Para). Control groups were 1) naïve animals, and 2) siblings of SE rats receiving only LiCl and paraldehyde (LiCl/Para). The expression profile of GRIA2A mRNA was determined via qPCR, and GluA2 protein levels were measured by western blotting. The analysis was performed at 3h (protein levels), and then 3-, 6-, 13-, and 60days, following LiCl/Pilo-SE or LiCl/Para injection (i.e. at P12, P15, P18, P25, P72 respectively). Six different brain regions were analyzed: frontal (CXFR), parietal (CXPAR), and occipital (CXOC) cortex, dorsal (HD) and ventral (HV) hippocampus, and thalamus (TH). There was a significant increase in GRIA2A mRNA expression in the CXFR, CXPAR, and CXOC of P18 SE animals. In CXFR and HD, increased expression of GluA2 AMPAR subunit protein was detected, as well as a surge in GRIA2A mRNA and GluA2 protein expression especially at P18. In HD the surge was detected not only during development (P18), but also later in life (P72). Since high levels of GluA2 can be neuroprotective (by decreasing Ca(2+) permeability), our data suggest that the neocortex and dorsal hippocampus are able to activate endogenous antiepileptic mechanisms. A marked decrease in the overall expression of GluA2 protein in the HV in the LiCl/Pilo-SE and LiCl/Para rats, suggests that the HV is predisposed to excitotoxicity, not only during development, but even in adulthood. Interestingly, LiCl in combination with paraldehyde can also strongly alter the normal ontogeny of GRIA2A mRNA as well as GluA2 subunit protein expression.

• Klíčová slova
• AMPA, Development, Expression, GRIA2A, GluA2, LiCl, Pilocarpine, Status epilepticus, Subunit,
• MeSH
• AMPA receptory genetika   metabolismus   MeSH
• chlorid lithný toxicita   MeSH
• fluoresceiny farmakokinetika   MeSH
• konvulziva toxicita   MeSH
• krysa rodu Rattus MeSH
• messenger RNA metabolismus   MeSH
• modely nemocí na zvířatech MeSH
• mozek účinky léků   růst a vývoj   metabolismus   MeSH
• novorozená zvířata MeSH
• pilokarpin toxicita   MeSH
• potkani Wistar MeSH
• status epilepticus chemicky indukované   metabolismus   patologie   MeSH
• věkové faktory MeSH
• vývojová regulace genové exprese účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• AMPA receptory MeSH
• chlorid lithný MeSH
• fluoresceiny MeSH
• fluoro jade MeSH Prohlížeč
• glutamate receptor ionotropic, AMPA 2 MeSH Prohlížeč
• konvulziva MeSH
• messenger RNA MeSH
• pilokarpin MeSH

The mammalian circadian system consists of a major circadian pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus and peripheral clocks in the body, including brain structures. The SCN depends on glutamatergic neurotransmission for transmitting signals from the retina, and it exhibits spontaneous 24-h rhythmicity in neural activity. The aim of this work was to evaluate the degree and circadian rhythmicity of AMPA receptor GluA2 subunit R/G editing and alternative flip/flop splicing in the SCN and other brain structures in Wistar rats. Our data show that the circadian rhythmicity in the SCN's GluA2 mRNA level was highest at dawn, while the circadian rhythm in R/G editing peaked at CT10 and the rhythmic flip varied with the acrophase at the late subjective night. The circadian rhythmicity was confirmed for R/G editing and splicing in the CA3 hippocampal area, and rhythmic variation of the flip isoform was also measured in the olfactory bulbs and cerebellum. The correlations between the R/G editing and alternative flip/flop splicing revealed a structure-dependent direction. In the hippocampus, the edited (G)-form level was positively correlated with the flip variant abundance, in accord with published data; by contrast, in the SCN, the flip variant was in associated more with the unedited (R) form. The edited (G) form and flop isoform also predominated in the retina and cerebellum.

• Klíčová slova
• Circadian clock, GluA2 subunit, R/G editing, Rat, Suprachiasmatic nucleus,
• MeSH
• AMPA receptory genetika   metabolismus   MeSH
• cirkadiánní rytmus genetika   MeSH
• editace RNA genetika   MeSH
• exony genetika   MeSH
• krysa rodu Rattus MeSH
• messenger RNA genetika   metabolismus   MeSH
• nucleus suprachiasmaticus metabolismus   MeSH
• posttranskripční úpravy RNA genetika   MeSH
• potkani Wistar MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• AMPA receptory MeSH
• glutamate receptor ionotropic, AMPA 2 MeSH Prohlížeč
• messenger RNA MeSH

Kainate receptors play a crucial role in mediating synaptic transmission within the central nervous system. However, the lack of selective pharmacological tool compounds for the GluK3 subunit represents a significant challenge in studying these receptors. Recently presented compound 1 stands out as a potent antagonist of GluK3 receptors, exhibiting nanomolar affinity at GluK3 receptors and strongly inhibiting glutamate-induced currents at homomeric GluK1 and GluK3 receptors in HEK293 cells with Kb values of 65 and 39 nM, respectively. This study presents the synthesis of two potent GluK3-preferring iodine derivatives of compound 1, serving as precursors for radiolabelling. Furthermore, we demonstrate the optimisation of dehalogenation conditions using hydrogen and deuterium, resulting in [2H]-1, and demonstrate the efficient synthesis of the radioligand [3H]-1 with a specific activity of 1.48 TBq/mmol (40.1 Ci/mmol). Radioligand binding studies conducted with [3H]-1 as a radiotracer at GluK1, GluK2, and GluK3 receptors expressed in Sf9 and rat P2 membranes demonstrated its potential applicability for selectively studying native GluK3 receptors in the presence of GluK1 and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-blocking ligands.

• Klíčová slova
• ionotropic glutamate receptors, quinoxaline‐2,3‐diones, tritium labelling,
• MeSH
• AMPA receptory chemie   metabolismus   MeSH
• deuterium MeSH
• HEK293 buňky MeSH
• krysa rodu Rattus MeSH
• kyselina glutamová * MeSH
• lidé MeSH
• receptory kyseliny kainové * chemie   metabolismus   MeSH
• tritium MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• AMPA receptory MeSH
• deuterium MeSH
• kyselina glutamová * MeSH
• receptory kyseliny kainové * MeSH
• tritium MeSH

Glutamate is the main excitatory neurotransmitter in the brain and ionotropic glutamate receptors mediate the majority of excitatory neurotransmission (Dingeldine et al. 1999). The high level of glutamatergic excitation allows the neonatal brain (the 2(nd) postnatal week in rat) to develop quickly but it also makes it highly prone to age-specific seizures that can cause lifelong neurological and cognitive disability (Haut et al. 2004). There are three types of ionotropic glutamate receptors (ligand-gated ion channels) named according to their prototypic agonists: N-methyl-D-aspartate (NMDA), 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) and kainate (KA). During early stages of postnatal development glutamate receptors of NMDA and AMPA type undergo intensive functional changes owing to modifications in their subunit composition (Carter et al. 1988, Watanabe et al. 1992, Monyer et al. 1994, Wenzel et al. 1997, Sun et al. 1998, Lilliu et al. 2001, Kumar et al. 2002, Matsuda et al. 2002, Wee et al. 2008, Henson et al. 2010, Pachernegg et al. 2012, Paoletti et al. 2013). Participation and role of these receptors in mechanisms of seizures and epilepsy became one of the main targets of intensive investigation (De Sarro et al. 2005, Di Maio et al. 2012, Rektor 2013). LiCl/Pilocarpine (LiCl/Pilo) induced status epilepticus is a model of severe seizures resulting in development temporal lobe epilepsy (TLE). This review will consider developmental changes and contribution of NMDA and AMPA receptors in LiCl/Pilo model of status epilepticus in immature rats.

• MeSH
• AMPA receptory metabolismus   MeSH
• krysa rodu Rattus MeSH
• mozek patofyziologie   MeSH
• nervový přenos * MeSH
• neurony metabolismus   MeSH
• novorozená zvířata MeSH
• receptory N-methyl-D-aspartátu metabolismus   MeSH
• stárnutí * MeSH
• status epilepticus patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• AMPA receptory MeSH
• receptory N-methyl-D-aspartátu MeSH

Adar2-/- mice are a widely used model for studying the physiological consequences of reduced RNA editing. These mice are viable only when the Q/R editing site of the Gria2 subunit of the AMPA receptor is constitutively mutated to the codon for arginine, and Gria2R/R mice often serve as the sole control for Adar2-/- mice. Our study aimed to investigate whether ADAR2 inactivity and the Gria2R/R phenotype affect the rhythmicity of the circadian clock gene pattern and the expression of Gria1 and Gria2 subunits in the suprachiasmatic nucleus (SCN), hippocampus, parietal cortex and liver. Our data show that Gria2R/R mice completely lost circadian rhythmicity in the hippocampus compared to Adar2-/- mice. Compared to C57BL/6J mice, the expression profiles in the hippocampus and parietal cortex of Gria2R/R mice differ to the same extent as in Adar2-/-. No alterations were detected in the circadian profiles in the livers. These data suggest that the natural gradual postnatal increase in the editing of the Q/R site of the Gria2 subunit may be important for the development of circadian clockwork in some brain structures, and the use of Gria2R/R mice as the only control to Adar2-/- mice in the experiments dependent on the hippocampus and parietal cortex should therefore be considered.

• Klíčová slova
• Adar2, Circadian rhythms, Gria2, Hippocampus, Mice, Suprachiasmatic nucleus,
• MeSH
• adenosindeaminasa genetika   metabolismus   MeSH
• cirkadiánní rytmus * MeSH
• exprese genu MeSH
• hipokampus metabolismus   MeSH
• mozek * metabolismus   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nucleus suprachiasmaticus metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ADAR2 protein, mouse MeSH Prohlížeč
• adenosindeaminasa MeSH
• glutamate receptor ionotropic, AMPA 2 MeSH Prohlížeč

The effect of lesions induced by bilateral intracerebroventricular (i.c.v.) injection of quinolinate (250 nmol of QUIN/ventricle), a selective N-methyl-D-aspartate (NMDA) receptor agonist, on [3H]glutamate ([3H]Glu) binding to the main types of both ionotropic and metabotropic glutamate receptors (iGluR and mGluR) was investigated in synaptic membrane preparations from the hippocampi of 50-day-old rats. The membranes from QUIN injured brains revealed significantly lowered binding in iGluR (by 31%) as well as in mGluR (by 22%) as compared to the controls. Using selected glutamate receptor agonists as displacers of [3H]Glu binding we found that both the NMDA-subtype of iGluR and group I of mGluR are involved in this decrease of binding. Suppression of nitric oxide (NO) production by N(G)-nitro-L-arginine (50 nmol of NARG/ventricle) or the increase of NO generation by 3-morpholinylsydnoneimine (5 nmol of SIN-1/ventricle) failed to alter [3H]Glu or [3H]CPP (3-((D)-2-carboxypiperazin-4-yl)-[1,2-(3)H]-propyl-1-phosphonic acid; NMDA-antagonist) binding declines caused by QUIN-lesions. Thus, our findings indicate that both the NMDA-subtype of iGluR and group I of mGluR are susceptible to the QUIN-induced neurodegeneration in the rat hippocampus. However, the inhibition of NO synthesis did not reveal any protective action in the QUIN-evoked, NMDA-receptor mediated decrease of [3H]Glu binding. Therefore, the additional mechanisms of QUIN action, different from direct NMDA receptor activation/NO production (e.g. lipid peroxidation induced by QUIN-Fe-complexes) cannot be excluded.

• MeSH
• agonisté excitačních aminokyselin farmakologie   MeSH
• buněčná membrána metabolismus   MeSH
• degenerace nervu chemicky indukované   metabolismus   patologie   MeSH
• donory oxidu dusnatého farmakologie   MeSH
• hipokampus metabolismus   patologie   MeSH
• kompetitivní vazba MeSH
• krysa rodu Rattus MeSH
• kyselina alfa-amino-3-hydroxy-5-methyl-4-isoxazolpropionová farmakologie   MeSH
• kyselina chinolinová MeSH
• kyselina chischalová farmakologie   MeSH
• kyselina glutamová farmakokinetika   MeSH
• kyselina kainová farmakologie   MeSH
• molsidomin analogy a deriváty   farmakologie   MeSH
• N-methylaspartát farmakologie   MeSH
• nitroarginin farmakologie   MeSH
• potkani Wistar MeSH
• synthasa oxidu dusnatého antagonisté a inhibitory   metabolismus   MeSH
• tritium 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
• agonisté excitačních aminokyselin MeSH
• donory oxidu dusnatého MeSH
• kyselina alfa-amino-3-hydroxy-5-methyl-4-isoxazolpropionová MeSH
• kyselina chinolinová MeSH
• kyselina chischalová MeSH
• kyselina glutamová MeSH
• kyselina kainová MeSH
• linsidomine MeSH Prohlížeč
• molsidomin MeSH
• N-methylaspartát MeSH
• nitroarginin MeSH
• synthasa oxidu dusnatého MeSH
• tritium MeSH

Specific [3H]glutamate binding to synaptic membranes from the cerebral cortex and hippocampus of 7-, 12- and 18-day-old rats was examined, both in control animals and during seizures induced by homocysteine. In the cerebral cortex a transient peak of glutamate binding was observed in 7-day-old group, whereas in the hippocampus it occurred in 12-day-old animals. Total specific [3H]glutamate binding was not influenced by preceding seizure activity in either of the age groups and both the studied regions. NMDA- and QA-sensitive glutamate bindings represent the highest portion of the total binding. Moreover, NMDA-sensitive binding in the cerebral cortex of 7-day-old rats is significantly higher as compared to the two more mature groups. The proportion of individual receptor subtypes on total binding in each age group was not influenced by preceding seizure activity. However, NMDA-sensitive binding in the hippocampus of 12-day-old rats, sacrificed during homocysteine-induced seizures, was significantly increased as compared to corresponding controls. In contrast to the effect of NMDA, AMPA, kainate and quisqualate which displaced to a different extent [3H]glutamate binding, homocysteine had no effect when added to membrane preparations. Similarly, [3H]CPP and [3H]AMPA bindings were not affected in the presence of homocysteine. It thus seems unlikely that homocysteine is an effective agonist for conventional ionotropic glutamate receptors. Its potential activity at some of the modulatory sites at the NMDA receptor channel complex or at metabotropic receptors has to be clarified in further experiments.

• MeSH
• analýza rozptylu MeSH
• hipokampus růst a vývoj   metabolismus   MeSH
• homocystein MeSH
• krysa rodu Rattus MeSH
• kyselina alfa-amino-3-hydroxy-5-methyl-4-isoxazolpropionová metabolismus   MeSH
• kyselina chischalová metabolismus   MeSH
• kyselina glutamová metabolismus   MeSH
• kyselina kainová metabolismus   MeSH
• mozková kůra růst a vývoj   metabolismus   MeSH
• N-methylaspartát metabolismus   MeSH
• potkani Wistar MeSH
• referenční hodnoty MeSH
• stárnutí metabolismus   MeSH
• synaptické membrány metabolismus   MeSH
• tritium MeSH
• vazebná místa MeSH
• záchvaty chemicky indukované   metabolismus   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
• homocystein MeSH
• kyselina alfa-amino-3-hydroxy-5-methyl-4-isoxazolpropionová MeSH
• kyselina chischalová MeSH
• kyselina glutamová MeSH
• kyselina kainová MeSH
• N-methylaspartát MeSH
• tritium MeSH

Cortical glial cells contain both ionotropic and metabotropic glutamate receptors. Despite several efforts, a comprehensive analysis of the entire family of glutamate receptors and their subunits present in glial cells is still missing. Here, we provide an overall picture of the gene expression of ionotropic (AMPA, kainate, NMDA) and the main metabotropic glutamate receptors in cortical glial cells isolated from GFAP/EGFP mice before and after focal cerebral ischemia. Employing single-cell RT-qPCR, we detected the expression of genes encoding subunits of glutamate receptors in GFAP/EGFP-positive (GFAP/EGFP(+)) glial cells in the cortex of young adult mice. Most of the analyzed cells expressed mRNA for glutamate receptor subunits, the expression of which, in most cases, even increased after ischemic injury. Data analyses disclosed several classes of GFAP/EGFP(+) glial cells with respect to glutamate receptors and revealed in what manner their expression correlates with the expression of glial markers prior to and after ischemia. Furthermore, we also examined the protein expression and functional significance of NMDA receptors in glial cells. Immunohistochemical analyses of all seven NMDA receptor subunits provided direct evidence that the GluN3A subunit is present in GFAP/EGFP(+) glial cells and that its expression is increased after ischemia. In situ and in vitro Ca(2+) imaging revealed that Ca(2+) elevations evoked by the application of NMDA were diminished in GFAP/EGFP(+) glial cells following ischemia. Our results provide a comprehensive description of glutamate receptors in cortical GFAP/EGFP(+) glial cells and may serve as a basis for further research on glial cell physiology and pathophysiology.

• Klíčová slova
• Astrocytes, Calcium imaging, MCAo, NG2 glia, Single-cell RT-qPCR,
• MeSH
• gliový fibrilární kyselý protein analýza   biosyntéza   MeSH
• glutamátové receptory analýza   biosyntéza   MeSH
• ischemie mozku metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• mozková kůra chemie   metabolismus   MeSH
• myši transgenní MeSH
• myši MeSH
• neuroglie chemie   metabolismus   MeSH
• receptory N-methyl-D-aspartátu analýza   biosyntéza   MeSH
• zelené fluorescenční proteiny analýza   biosyntéza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• enhanced green fluorescent protein MeSH Prohlížeč
• glial fibrillary astrocytic protein, mouse MeSH Prohlížeč
• gliový fibrilární kyselý protein MeSH
• glutamátové receptory MeSH
• receptory N-methyl-D-aspartátu MeSH
• zelené fluorescenční proteiny MeSH

Spermine and related polyamines have been shown to be endogenous regulators of several ion channel types including ionotropic glutamate receptors. The effect of spermine on N-methyl-d-aspartate (NMDA) receptors in cultured rat hippocampal neurons was studied using single-channel and whole-cell patch clamp recordings. Intracellular spermine resulted in the dose-dependent inhibition of NMDA-induced responses. Spermine reversibly inhibited the single NMDA receptor channel activity in inside-out patches suggesting a membrane-delimited mechanism of action. Open probability of NMDA receptor channels was decreased in a dose-dependent manner. Mechanism of spermine-induced inhibition of NMDA receptor was different from that of intracellular Ca(2+)-induced NMDA receptor inactivation. Both pharmacological studies and single channel analysis indicate that in contrast to the effect of extracellular spermine the intracellular spermine effect is not dependent on the NMDA receptor subunit composition. We propose that intracellular spermine has a direct inhibitory effect on NMDA receptors that is different from calcium-induced NMDA receptor inactivation and spermine-induced voltage-dependent inhibition of AMPA/kainate receptors. Spermine-induced tonic change in the open probability of NMDA receptor channels may play a role in mechanisms underlying short-term changes in the synaptic efficacy.

• MeSH
• elektrofyziologie MeSH
• hipokampus metabolismus   MeSH
• intracelulární tekutina chemie   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• metoda terčíkového zámku MeSH
• neurony metabolismus   MeSH
• novorozená zvířata MeSH
• receptory N-methyl-D-aspartátu účinky léků   metabolismus   MeSH
• spermin metabolismus   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptory N-methyl-D-aspartátu MeSH
• spermin MeSH

Introduction: Perampanel is an antiepileptic drug approved in the USA and Europe as monotherapy and adjunctive therapy for focal onset seizures and as adjunctive therapy for generalized tonic-clonic seizures. Areas covered: This an overview of animal data, pharmacokinetics, and clinical data published on Perampanel indexed in PubMed. Expert opinion: Pharmacological studies suggest that perampanel acts via noncompetitive antagonism of the ionotropic AMPA receptor of glutamate. The efficacy of perampanel has been shown in animal models of epilepsy and Phase II/III clinical trials. Efficacy and safety have been evaluated in the phase III trials of adjunctive treatment of focal epilepsy with median focal onset seizure reduction rates of 23% for 4 mg/d, 26-31% for 8 mg/day, and 18-35% for 12 mg/day. Fifty percent responder rates were 29% for 4 mg/day, 33-38% for 8 mg/day, and 34-36% for 12 mg/day. A pivotal Phase III trial in generalized onset tonic-clonic seizures showed a median seizure reduction by 76.5% (8 mg) versus 38.4% placebo and 50% seizure responder rate of 64.2% versus 30.9% placebo. Perampanel showed good safety and tolerability profile across 2-12 mg doses. Perampanel as a broad-spectrum antiepileptic drug has a potential to be an alternative treatment of multiple types of epileptic seizures.

• Klíčová slova
• AMPA receptor antagonist, adjunctive therapy, anti-seizure drug, focal seizures, generalized tonic-clonic seizures, monotherapy,
• MeSH
• antikonvulziva aplikace a dávkování   farmakologie   MeSH
• epilepsie generalizovaná farmakoterapie   MeSH
• epilepsie parciální farmakoterapie   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• nitrily MeSH
• pyridony aplikace a dávkování   farmakologie   MeSH
• záchvaty farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antikonvulziva MeSH
• nitrily MeSH
• perampanel MeSH Prohlížeč
• pyridony MeSH