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Neues Opioid-Analgetikum steht vor Durchbruch

Die Pharmazie steht in der Entwicklung eines neuen analgetisches Arzneistoffs vor einem Durchbruch. Ein Forscherteam um Dr. Aasish Manglik Stanford und Nobelpreisträger Prof. Dr. Brian Koblika von der Stanford University, konnte mit ihren Forschungen zur Entwicklung eines ohne Atemdepression und Abhängigkeit auslösenden Opium -Analgetikum erste Erfolge in entsprechenden Modellversuchen erzielen. Die Ergebnisse mit der Leitsubstanz PZM21 wurden im Fachjournal Nature veröffentlicht. In einem Testdurchlauf mit Mäusen zeigte die Gabe von PZM21 in einer 40mg/kg Dosierung dieselbe Wirkung wie 10mg/kg Morphin, jedoch länger schmerzstillend und ohne Ausfall schmerzbedingter Reflexe. Diese separate Wirkung bezeichnete Manglik laut einer Mitteilung der Friedrich-Alexander-Universität Erlangen-Nürnberg als einzigartig unter den Opioid-Analgetika. Opioide entfalten ihre Wirkung durch die über die Bindung an die Gi-gekoppelten µ-Opioid-Rezeptoren und können zwei Signalkaskaden auslösen. Neben der Aktivierung des Gi-Proteins, welches über eine Verminderung der cAMP-Konzentration zur Analgesie führt, kann diese Signaltransduktion ihren Weg auch Gi-Protein-unabhängig über ß-Arrestin nehmen. Diese Konstellation steht nach aktuellen Erkenntnissen in Zusammenhang mit den Nebenwirkungen. Die Umgehung der ß-Arrestin Aktivierung und die Suche nach einem Wirkstoff ohne Opioid-Struktur, der sich funktionell an das G-Protein richtet ist seither Gegenstand der Analgetikum-Forschung. In ihren Untersuchungen screenten die Forscher mittels Docking-Verfahren über drei Millionen potenzielle Wirkstoffe bei dem die Substanzen virtuell an die Bindungstasche des Rezeptors angekoppelt wurden. Die Untersuchung 23 erfolgversprechender Moleküle, die Auswahl der Leitsubstanz und die Optimierung der Wirksamkeit führten zum Resultat PZM21. Jedoch stehen bis zur Marktreife noch eine Reihe von klinische Studien und Forschungsarbeiten bevor.

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