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Featured researches published by Károly Tihanyi.


Brain Research | 2014

Estradiol and isotype-selective estrogen receptor agonists modulate the mesocortical dopaminergic system in gonadectomized female rats

Miklós Sárvári; Levente Deli; Pál Kocsis; László Márk; Gábor Maász; Erik Hrabovszky; Imre Kalló; Dávid Gajári; Csaba Vastagh; Balazs Sumegi; Károly Tihanyi; Zsolt Liposits

The mesocortical dopaminergic pathway projecting from the ventral tegmental area (VTA) to the prefrontal cortex (PFC) contributes to the processing of reward signals. This pathway is regulated by gonadal steroids including estradiol. To address the putative role of estradiol and isotype-selective estrogen receptor (ER) agonists in the regulation of the rodent mesocortical system, we combined fMRI, HPLC-MS and qRT-PCR techniques. In fMRI experiments adult, chronically ovariectomized rats, treated with either vehicle, estradiol, ERα agonist 16α-lactone-estradiol (LE2) or ERβ agonist diarylpropionitrile (DPN), received a single dose of d-amphetamine-sulphate (10mg/kg, i.p.) and BOLD responses were monitored in the VTA and the PFC. Ovariectomized rats showed no significant response to amphetamine. In contrast, the VTA of ER agonist-substituted ovariectomized rats showed robust amphetamine-evoked BOLD increases. The PFC of estradiol-replaced animals was also responsive to amphetamine. Mass spectroscopic analysis of dopamine and its metabolites revealed a two-fold increase in both dopamine and 3,4-dihydroxyphenylacetic acid content of the PFC in estradiol-replaced animals compared to ovariectomized controls. qRT-PCR studies revealed upregulation of dopamine transporter and dopamine receptor in the VTA and PFC, respectively, of ER agonist-treated ovariectomized animals. Collectively, the results indicate that E2 and isotype-selective ER agonists can powerfully modulate the responsiveness of the mesocortical dopaminergic system, increase the expression of key genes related to dopaminergic neurotransmission and augment the dopamine content of the PFC. In a broader sense, the findings support the concept that the manifestation of reward signals in the PFC is dependent on the actual estrogen milieu of the brain.


Brain Research Bulletin | 2013

Effect of tolperisone on the resting brain and on evoked responses, an phMRI BOLD study.

Pál Kocsis; Dávid Gajári; Levente Deli; Krisztina Zsedrovitsné Gőcze; Zsófia Pozsgay; Károly Tihanyi

Tolperisone is a voltage gated sodium channel blocker, centrally acting muscle relaxant drug, with a very advantageous side effect profile. Like other sodium channel blockers, it has weak affinity to the resting state and high affinity to the open/inactivated state of the channel. In this paper, its effect on BOLD responses in rat brain were elucidated both on the resting brain and paw stimulation evoked BOLD responses. Tolperisone did not exert any visible effect on resting brain, but strongly inhibited the paw stimulation evoked BOLD responses, showing somewhat higher efficacy in brain areas involved in pain sensation. This finding is in a good agreement with its sodium channel blocking profile. In the resting brain, most of the channels are in resting state. Electric train stimuli of the paw results in over activated neurons, where most sodium channels are in open or inactivated state. These data suggest that the very advantageous profile of tolperisone can be explained by its selective action on open or inactivated sodium channels of over-activated neurons in various brain regions rather than by a selective effect in the spinal cord as suggested previously.


Neurochemistry International | 2007

The new 2,3-benzodiazepine derivative EGIS-8332 inhibits AMPA/kainate ion channels and cell death

Miklos Vegh; Attila Kovács; Gabor Kovacs; Geza Szabo; Károly Tihanyi; Laszlo Gabor Harsing; György Lévay

We observed in vitro neuroprotective and AMPA/kainate receptor antagonist effects of the new 2,3-benzodiazepine derivative EGIS-8332 (R,S-1-(4-aminophenyl)-7,8-methylenedioxy-4-cyano-4-methyl-3-N-acetyl-5H-3,4-dihydro-2,3-benzodiazepine) using the lactate dehydrogenase (LDH) release assay and patch clamp recordings on primary cultures of rat embryonic telencephalon neurons exposed to AMPA/kainate receptor agonists. EGIS-8332 potently decreased alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate induced LDH release (IC(50)=5.2+/-0.4 and 7.4+/-1.3 microM, respectively) from the cells. Whole-cell patch clamp studies carried out on the ionotropic glutamate receptors N-methyl D-aspartate (NMDA), as well as AMPA (and kainate) in cultured telencephalon neurons verified that EGIS-8332 blocked steady state responses to AMPA and kainate (IC(50)=1.7+/-0.4 and 6.2+/-1.6 microM, respectively), but hardly influenced currents evoked by NMDA. EGIS-8332 also inhibited kainate-evoked response in CHO cells expressing the flop variant of GluR1 receptor and, in cerebellar Purkinje cells at similar efficiency. The stereoselectivity of the inhibitory site is established by the clearly dissimilar inhibitory potency of the enantiomer components of EGIS-8332 differing in the configuration of methyl and cyano substituents on carbon C(4): the R(-) enantiomer was found to be the efficient species. This finding suggests that the inhibitory interaction between the channel protein and drug is promoted by presence of the C(4) methyl group. The inhibition of the AMPA/kainate ion channels by EGIS-8332 is non-competitive, not use dependent, and depends neither on the closed/open state of the channel, nor the membrane potential. These findings suggest an allosteric mechanism for the inhibition. These in vitro observations suggest that the compound might be useful in the treatments of certain acute and chronic neurological syndromes initiated by derangements of ionotropic glutamate receptor function.


Bioorganic & Medicinal Chemistry Letters | 2002

Synthesis and evaluation of 5-HT2A and 5-HT2C receptor binding affinities of novel pyrimidine derivatives

Daniel Bozsing; Ildikó Rátzné Simonek; Gyula Simig; Ivan Jakoczi; Istvan Gacsalyi; Gyoergy Levay; Károly Tihanyi; Eva Schmidt

In an effort to find potential anxiolytic and/or antipsychotic agents with selective 5-HT(2C) affinity a series of new pyrimidine derivatives was prepared and the binding affinities for 5-HT(2A) and 5-HT(2C) receptors were determined.


Archive | 2000

Piperazinylalkylthiopyrimidine derivatives, pharmaceutical compositions containing the same, and a process for the preparation of the active substance

Ildikó Rátzné Simonek; Daniel Bozsing; Gábor Németh; Gyula Simig; László Poszávácz; Ivan Jakoczi; György Lévay; Istvan Gacsalyi; Károly Tihanyi; Janos Wellmann; Andras Egyed


Archive | 1998

1,3-DIOXOLO/4,5-H//2,3/BENZODIAZEPINE DERIVATIVES AS AMPA/KAINATE RECEPTOR INHIBITORS

Jozsef Barkoczy; Judit Cselenyak; Zoltan Ratkai; Gyula Simig; Laszlo Balazs; Imre Doman; Nagy Peter Kotay; Zoltan Greff; Péter Seres; Geza Szabo; Istvan Gacsalyi; Gabor Gigler; Istvan Gyertyan; György Lévay; Attila Kovács; Annamária Simó; Tamás Szabados; Andras Egyed; Miklos Vegh; Károly Tihanyi


Archive | 2000

Novel piperazinylalkylthiopyrimidine derivatives, pharmaceutical compositions containing the same and a process for the preparation of the novel compounds

Daniel Bozsing; Andras Egyed; Istvan Gacsalyi; Ivan Jakoczi; György Lévay; Gábor Németh; László Poszávácz; Simonek Ildiko Ratzne; Gyula Simig; Károly Tihanyi; János Wellman


Archive | 1998

8-substituted-9H-1,3-dioxolo/4,5-h//2,3/benzodiazepine derivatives, as AMPA/kainate receptor inhibitors

Laszlo Balazs; Jozsef Barkoczy; Imre Doman; Andras Egyed; Istvan Gacsalyi; Gabor Gigler; Zoltan Greff; Istvan Gyertyan; Peter Kotay Nagy; Attila Kovács; György Lávay; Zoltan Ratkai; Péter Seres; Gyula Simig; Annamária Simó; Tamás Szabados; Geza Szabo; Károly Tihanyi; Miklos Vegh; Geza Schneider; Judit Cselenyak


Archive | 1996

1-(Hetero)Arylvinyl-5H-2,3-benzodiazepine derivatives useful for the treatment of central nervous system disorders, and benzopyrylium intermediates for their preparation

Pal Vago; Jozsef Reiter; Istvan Gyertyan; Istvan Gacsalyi; Andras Bilkei-Gorzo; Andras Egyed; Ferenc Andrasi; Anna Bakonyi; Pál Dr. Berzsensyi; Peter Botka; Tamas Hamori; Haskane Cecilia Salamon; Edit Dr. Horváth; Katalin Dr. Horváth; Jeno Korosi; Gyorgyne Mate; Imre Moravcsik; Eszter Szentkuti; Gabor Zolyomi; Gabor Blasko; Kazone Klara Daroczi; Gyula Simig; Károly Tihanyi; Judit Bajnogel

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