Τόμος 13 (1995) – Τεύχος 3 – Άρθρο 1 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 13 (1995) – Issue 3 – Article 1 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

Από | | Αλέξανδρος Μακρυγιάννης - Alexandros Makriyannis, Άρθρο - Article, Δημήτρης Παπαχατζής, D. Papahatjis, Ευθυμία Θεοδωροπούλου - Efthimia Theodoropoulou, Θε­ρα­πεί­α Κου­ρου­λή,T. Kourouli, Θωμάς Μαυρομούστακος - Thomas Mavromoustakos, Πλήρες Κείμενο στα Ελληνικά - Full Text in Greek

 

Τίτλος – Title

Πρόσφα­τες Ε­ξε­λί­ξεις στο Πε­δί­ο των Καν­να­βι­νο­ει­δών. Σύν­θε­ση Πρω­τό­τυ­πων Α­να­λό­γων και Αλ­λη­λε­πι­δρά­σεις τους με Μεμ­βρά­νες

Recent Advances in the Field of Cannabinoids: Synthesis of Novel Analogs and their Interactions with Membranes
Συγγραφέας – Author

Θω­μάς Μαυ­ρο­μού­στα­κος1, Δη­μή­τρης Πα­πα­χα­τζής1, Θε­ρα­πεί­α Κου­ρου­λή1, Ευ­θυ­μί­α Θε­ο­δω­ρο­πού­λου1 και Α­λέ­ξαν­δρος Μα­κρυ­γιάν­νης2

1 Ε­θνι­κό ΄Ι­δρυ­μα Ε­ρευ­νών, Ιν­στι­τού­το Ορ­γα­νι­κής και Φαρ­μα­κευ­τι­κής Χη­μεί­ας, Βα­σι­λέ­ως Κων­στα­ντί­νου 48, Α­θή­να 116 35, Ελλάς 2 Department of Pharmaceutical Sciences, Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269 USA

T. Mavromoustakos1, D. Papahatjis1,T. Kourouli1, E. Theodoropoulou1 and A. Makriyannis2

1 Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, Vas. Constantinou 48, 116 35 Athens, Greece 2 Department of Pharmaceutical Sciences, Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269 USA
Παραπομπή – Citation

Μαυ­ρο­μού­στα­κος,Θ.,  Πα­πα­χα­τζής, Δ.,  Κου­ρου­λή,Θ., Θε­ο­δω­ρο­πού­λου,Ε., Μα­κρυ­γιάν­νης,Α. : Πρόσφα­τες Ε­ξε­λί­ξεις στο Πε­δί­ο των Καν­να­βι­νο­ει­δών. Σύν­θε­ση Πρω­τό­τυ­πων Α­να­λό­γων και Αλ­λη­λε­πι­δρά­σεις τους με Μεμ­βρά­νες , Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 14 : 105-128 (1996)

Mavromoustakos,T.,  Papahatjis,D., Kourouli,T., Theodoropoulou,E., Makriyannis,A. : Recent Advances in the Field of Cannabinoids: Synthesis of Novel Analogs and their Interactions with Membranes, Epitheorese Klin. Farmakol. Farmakokinet. 14 : 105-128 (1996)
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Λέξεις κλειδιά – Keywords

Κανναβινοειδή, σύνθεση αναλόγων, αλληλεπιδράσεις με μεμβράνες

Cannabinoids, synthesis of novel analogs, interactions with membranes
Λοιποί Όροι – Other Terms

Άρθρο

Article
Περίληψη – Summary

Στο άρ­θρο αυτό γί­νε­ται σύ­ντο­μη α­να­σκό­πη­ση των τε­λευ­ταί­ων προ­ό­δων στο πεδί­ο των καν­να­βι­νο­ει­δών, με έμ­φα­ση στη σύν­θε­ση βιο­λο­γι­κώς δρα­στι­κών καν­να­βι­νο­ει­δών και στην αλ­λη­λε­πί­δρα­σή τους με λι­πο­ει­δείς δι­πλο­στοι­βά­δες. Συ­γκε­κρι­μέ­να, πε­ρι­γρά­φε­ται η σύν­θε­ση ο­δη­γών πρω­τότυ­πων μο­ρί­ων που ε­πε­τεύ­χθη σε άλ­λα ερ­γα­στή­ρια και στο δι­κό μας. Αυ­τές α­να­μέ­νε­ται να δώ­σουν και­νούρ­για ώ­θη­ση και πλη­ρο­φο­ρίες για το μη­χα­νι­σμό δρά­σης τους επά­νω στους υ­πο­δο­χείς. Ε­πει­δή οι μεμ­βρά­νες είναι πο­λύ­πλο­κα και α­στα­θή βιο­λο­γι­κά συ­στή­μα­τα, εί­ναι δύ­σκο­λο να με­λε­τη­θούν με μια α­πλή βιο­φυ­σι­κή μέ­θο­δο, γεγονός που απαιτεί συν­δυα­σμό πε­ρισ­σότε­ρων με­θό­δων για τη λήψη ο­λο­κλη­ρω­μέ­νης πλη­ρο­φο­ρί­ας. Για τη με­λέ­τη των αλ­λη­λε­πι­δρά­σε­ων πε­ρι­γρά­φο­νται τρεις βιο­φυ­σι­κές μέ­θο­δοι που χρη­σι­μο­ποι­ε­ί το ερ­γα­στή­ριο μας. Σαν πα­ρά­δειγ­μα της ι­κα­νό­τη­τας των με­θό­δων να α­νι­χνεύ­σουν δια­φο­ρε­τι­κές αλ­λη­λε­πι­δρά­σεις ε­νώ­σε­ων με πα­ρό­μοι­α χη­μι­κή δο­μή, με διαφορετική ό­μως βιο­λο­γι­κή δρα­στι­κό­τη­τα, α­να­φέ­ρε­ται αυτό της Δ8-τε­τρα­ϋ­δρο­καν­να­βι­νό­λης, που εμ­φα­νί­ζει ψυ­χο­μι­μη­τι­κές ι­διό­τη­τες και του μη δρα­στι­κού της αι­θέ­ρα Ο-μέ­θυ­λο-Δ8-τε­τρα­ϋ­δρο­καν­να­βι­νό­λη.

This article emphasizes the synthesis of some key analogs as well as the methods used to study cannabinoid:membrane interactions. The availability of the cannabimimetic analogs described here has provided new insights on the molecular requirements for cannabimimetic activity. Since membranes are characterized by complexity and inherent instability they do not lend themselves to a detailed analysis of their structure and dynamics by a single biophysical method. It is therefore, preferable to use jointly several experimental techniques for such studies. In this article, a combination of three techniques were used to study cannabinoid membrane interactions. A pair of analogs is chosen for this comparison which have a close structural resemblance but differ greatly in their biological activities. Specifically, Δ8-tetrahydrocannabinol (Δ8-THC) possesses a phenolic hydroxyl group and has psychotropic properties whereas its methylated analog Me-Δ8-tetrahydrocannabinol (Me-Δ8 -THC ) is biologically inactive. The review outlines how the three bio-hysical methods (DSC, X-ray, stationary and high resolution solid state NMR) can be used to demonstrate how the above two molecules interact differently with membrane bilayers, an observation which may explain at least in part their different biological properties. A discussion of the results is included as well as the molecular mechanism of a membrane based cannabinoid activity followed by a proposed model.
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