Τίτλος – Title
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Mη Πεπτιδικοί, Μικρομοριακοί Ανταγωνιστές (ΜΜΑ) της Εκλυτικής Ορμόνης της Κορτικοτροπίνης (CRH): Μελλοντικές Εφαρμογές στη Θεραπευτική Non-peptide, Micromolecular Αntagonists of Corticotrophin Releasing Hormone (CRH): Future applications in Therapeutics |
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Συγγραφέας – Author
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Ε. Κουϊμτζόγλου, Α. Χατζάκη, Α. Γραβάνης Εργαστήριο Φαρμακολογίας, Τμήμα Ιατρικής, Πανεπιστήμιο Κρήτης, Ηράκλειο 71110 E. Kouimtzoglou, A. Chatzaki, A. Gravanis University of Crete, Faculty of Medicine, Department of Basic Sciences, Laboratory of Pharmacology, Heraklion, Crete 71110 Greece |
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Παραπομπή – Citation
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Κουϊμτζόγλου,Ε., Χατζάκη,Α., Γραβάνης,Α. : Mη Πεπτιδικοί, Μικρομοριακοί Ανταγωνιστές (ΜΜΑ) της Εκλυτικής Ορμόνης της Κορτικοτροπίνης (CRH): Μελλοντικές Εφαρμογές στη Θεραπευτική, Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 19 : 158-167 (2001) Kouimtzoglou,E., Chatzaki,A., Gravanis,A. : Non-peptide, Micromolecular Αntagonists of Corticotrophin Releasing Hormone (CRH): Future applications in Therapeutics, Epitheorese Klin. Farmakol. Farmakokinet. 19: 158-167 (2001) |
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Ημερομηνία Δημοσιευσης – Publication Date
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13-03-2001 – 2001-03-13
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Γλώσσα Πλήρους Κειμένου –
Full Text Language |
Ελληνικά – Greek |
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Λέξεις κλειδιά – Keywords
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Μη-πεπτιδικοί μικρομοριακοί ανταγωνιστές, εκλυτική ορμόνη της κορτικοτροπίνης, άγχος, κατάθλιψη, φλεγμονή, αναπαραγωγή Non-peptide, micromolecular antagonists, corticotrophin releasing hormone, stress, depression, inflammation, reproduction
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Λοιποί Όροι – Other Terms
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Άρθρο Article |
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Περίληψη – Summary
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Η Εκλυτική Ορμόνη της Κορτικοτροπίνης (CRH) παράγεται κατ’ εξοχήν στον παρακοιλιακό πυρήνα του υποθαλάμου και αποτελεί πλειοτροπικό παράγοντα ρύθμισης πολλών κεντρικών και περιφερικών συστημάτων. Πράγματι η CRH κατέχει κεντρικό ρόλο στο συντονισμό των ενδοκρινικών και συμπεριφερικών αποκρίσεων στο άγχος, ενώ εμπλέκεται στην παθοφυσιολογία νευροψυχικών και νευροεκφυλιστικών ασθενειών, όπως η κατάθλιψη, η νευρογενής ανορεξία, η εξάρτηση και η νόσος του Alzheimer. Επιπλέον η CRH παράγεται περιφερικά στο Ανοσοποιητικό και Αναπαραγωγικό Σύστημα, εμπλεκόμενη σε φαινόμενα με φλεγμονώδη χαρακτηριστικά, όπως η νευρογενής φλεγμονή, η εμφύτευση της βλαστοκύστης και ο τοκετός. Πολύ πρόσφατα, ανεκαλύφθη σειρά μη πεπτιδικών μικρομοριακών ανταγωνιστών της CRH. Φαρμακολογικές μελέτες σε μοντέλα πειραματοζώων έχουν δείξει ότι οι ΜΜΑ ανταγωνιστές της CRH έχουν αγχολυτική και αντικαταθλιπτική δράση και δρουν ως ισχυροί αναστολείς της φλεγμονής, του πρόωρου τοκετού και της εμφύτευσης της βλαστοκύστης σε πολύ πρώιμα σταδία της εγκυμοσύνης. Τα ευρήματα αυτά έχουν οδηγήσει στις πρώτες κλινικές μελέτες των νέων αυτών μη πεπτιδικών ανταγωνιστών της CRH. The major source of CRH expression is the hypothalamic paraventricular nucleus, where the neuropeptide acts as a regulatory factor in multiple central and peripheral systems. Indeed, CRH plays a central role in the coordination of endocrine and behavioural responses to stress, whereas it is also involved in the pathophysiology of several neuropsychiatric and neurodegenerative diseases such as depression, anorexia nervosa, addiction and Alzheimer’s disease. In addition, CRH is expressed in the periphery and in particular in the immune and reproductive systems, where it is involved in phenomena of inflammatory characteristics such as neurogenic inflammation, embryo implantation and delivery. Very recently a new series of non-peptide micromolecular CRH antagonists (MMA) has been developed. Pharmacological studies on experimental animals have shown that MMA exert anti-depressive and anti-anxiety effects and act as inhibitors of inflammation, pre-term delivery and blastocyst implantation at the very early stages of gestation. These findings led to the first clinical studies evaluating the therapeutic value of the newly developed non-peptide CRH antagonists. |
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Αναφορές – References
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