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Vecsei L.,Hungarian Academy of Sciences | Vecsei L.,University of Szeged | Vecsei L.,MTA SZTE Neuroscience Research Group | Majlath Z.,University of Szeged | And 3 more authors.
Expert Opinion on Drug Safety | Year: 2015

Introduction: Migraine is a frequent, disabling primary headache disorder, whose pathomechanism is not yet fully understood. Prophylactic treatment is advisable for migraineurs with severe or highly frequent attacks, which impair the quality of life.Areas covered: The different types of prophylactic migraine drugs are discussed, with particular regard to potential adverse effects and safety issues. β-Adrenergic blockers, antiepileptic drugs and calcium-channel blockers are drugs widely used for migraine prevention, whereas complementary medicine and onabotulinumtoxin A can be used in selected cases.Expert opinion: The background of the recurrence and chronification of migraine attacks has not been fully clarified, and causative preventive therapy is therefore not currently available. The tolerability and adverse effects of the currently used medications often limit their use. β-Adrenergic receptor blockers may induce adverse cardiovascular events, whereas flunarizine is frequently associated with a weight gain and depression. As most migraine sufferers are young women of child-bearing age, the use of valproate is limited. Topiramate is associated with central nervous system-related side effects. There is a need for future development of pathomechanism-based preventive drugs, and personalized therapy tailored to the patient. © 2015 Informa UK, Ltd. Source

Rajda C.,University of Szeged | Majlath Z.,University of Szeged | Pukoli D.,University of Szeged | Vecsei L.,University of Szeged | Vecsei L.,MTA SZTE Neuroscience Research Group
International Journal of Molecular Sciences | Year: 2015

Multiple sclerosis is an inflammatory disease of the central nervous system, in which axonal transection takes place in parallel with acute inflammation to various, individual extents. The importance of the kynurenine pathway in the physiological functions and pathological processes of the nervous system has been extensively investigated, but it has additionally been implicated as having a regulatory function in the immune system. Alterations in the kynurenine pathway have been described in both preclinical and clinical investigations of multiple sclerosis. These observations led to the identification of potential therapeutic targets in multiple sclerosis, such as synthetic tryptophan analogs, endogenous tryptophan metabolites (e.g., cinnabarinic acid), structural analogs (laquinimod, teriflunomid, leflunomid and tranilast), indoleamine-2,3-dioxygenase inhibitors (1MT and berberine) and kynurenine-3-monooxygenase inhibitors (nicotinylalanine and Ro 61-8048). The kynurenine pathway is a promising novel target via which to influence the immune system and to achieve neuroprotection, and further research is therefore needed with the aim of developing novel drugs for the treatment of multiple sclerosis and other autoimmune diseases. © 2015 by the authors; licensee MDPI, Basel, Switzerland. Source

Dezsi L.,University of Szeged | Vecsei L.,University of Szeged | Vecsei L.,MTA SZTE Neuroscience Research Group
Expert Opinion on Investigational Drugs | Year: 2014

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. Non-dopaminergic neurotransmitter systems are also involved in its pathomechanism. The aim of the treatment is to improve the dopamine-deficient state and to alleviate the motor and the non-motor symptoms. Safinamide is an α-aminoamide derivative with a combined, dopaminergic and non-dopaminergic mode of action. Phase III clinical trials with safinamide, as add-on therapy to a dopamine agonist (DAA) and to levodopa (LD) in early and advanced stage PD, respectively, demonstrated an improvement of the motor symptoms. Areas covered: The review discusses the pharmacokinetic and pharmacodynamic properties of safinamide and provides an overview of the clinical trials conducted with safinamide in PD. A literature search was made in PubMed for safinamide, safinamide pharmacokinetics, PD treatment and monoamine oxidase-B inhibitors, and in PubMed and on the ClinicalTrials.gov site for clinical trials with safinamide in PD. Expert opinion: The place of safinamide in the therapy of PD is yet to be determined. However, the authors believe that safinamide is a valuable drug in the treatment of PD treatment with favorable pharmacokinetic and side-effect profiles. Data so far suggest that it can be used beneficially as add-on therapy both to DAAs in early PD and to LD in the later stages of the disease. © 2014 Informa UK, Ltd. Source

Torok R.,University of Szeged | Konya J.A.,University of Szeged | Zadori D.,University of Szeged | Veres G.,University of Szeged | And 4 more authors.
Cellular and Molecular Neurobiology | Year: 2015

Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1 alpha (PGC-1α) is involved in the regulation of mitochondrial biogenesis, respiration, and adaptive thermogenesis. The full-length PGC-1α (FL-PGC-1α) comprises multiple functional domains interacting with several transcriptional regulatory factors such as nuclear respiratory factors, estrogen-related receptors, and PPARs; however, a number of PGC-1α splice variants have also been reported recently. In this study, we examined the expression levels of FL-PGC-1α and N-truncated PGC-1α (NT-PGC-1α), a shorter but functionally active splice variant of PGC-1α protein, in N171-82Q transgenic and 3-nitropropionic acid-induced murine model of Huntington’s disease (HD). The expression levels were determined by RT-PCR in three brain areas (striatum, cortex, and cerebellum) in three age groups (8, 12, and 16 weeks). Besides recapitulating prior findings that NT-PGC-1α is preferentially increased in 16 weeks of age in transgenic HD animals, we detected age-dependent alterations in both models, including a cerebellum-predominant upregulation of both PGC-1α variants in transgenic mice, and a striatum-predominant upregulation of both PGC-1α variants after acute 3-nitropropionic acid intoxication. The possible relevance of this expression pattern is discussed. Based on our results, we assume that increased expression of PGC-1α may serve as a compensatory mechanism in response to mitochondrial damage in transgenic and toxin models of HD, which may be of therapeutic relevance. © 2014, Springer Science+Business Media New York. Source

Tajti J.,University of Szeged | Tuka B.,MTA SZTE Neuroscience Research Group | Botz B.,University of Pecs | Helyes Z.,University of Pecs | And 3 more authors.
CNS and Neurological Disorders - Drug Targets | Year: 2015

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors are widely distributed at different levels of the pain-processing pathway. Its action at the peripheral sensory nerve terminals has been found to be divergent; it can exert both pro- and anti-nociceptive effects, depending on the mode of administration (local or systemic) and the mechanism of the pain process (acute or chronic, inflammatory or neuropathic). In the central nervous system it exerts mainly neuronal excitation, leading to increased nociceptive signalling. Since the clinical data strongly suggest the involvement of PACAP in the pathophysiology of migraine, special emphasis is placed on examinations of its role and the mechanisms of activation of the trigeminovascular system. The intravenous administration of PACAP to migraineurs induces migraine-like headache and extracranial arterial dilatation. Furthermore, an increased PACAP concentration has been detected in the peripheral blood of patients during a migraine attack. Animal experiments have also revealed that PACAP elicits peripheral and central sensitization of the neuronal elements of the trigeminovascular system and evokes meningeal vasodilatation. This review summarizes data relating to the expression of PACAP and its receptors, and the main effects and mechanisms in the nociceptive pathways, with special emphasis on migraine. It is clear that PACAP plays an excitatory role in migraine, but its target and signalling pathways have not yet been elucidated due to the lack of non-peptide, selective agonists and antagonists. Identification of its up- and downstream regulations and receptorial molecular mechanisms might open up future perspectives for the development of novel analgesic drugs. © 2015 Bentham Science Publishers. Source

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