A2A-selective adenosine receptor antagonists: Development of water-soluble prodrugs and a new tritiated radioligand
✍ Scribed by Christa E. Müller; Roland Sauer; Yuris Maurinsh; Rosa Huertas; Friederike Fülle; Karl-Norbert Klotz; Jens Nagel; Wolfgang Hauber
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 214 KB
- Volume
- 45
- Category
- Article
- ISSN
- 0272-4391
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✦ Synopsis
A 2A adenosine receptor (AR) antagonists are promising new drugs for the treatment of Parkinson's disease. Further potential therapeutic indications for A 2A AR antagonists include dementias, ischemias, and pain. Potent, selective A 2A AR antagonists have been developed, but their generally low water solubility is a major problem for conducting in vivo experiments. We developed a water-soluble phosphate prodrug (MSX-3) of a potent, selective A 2A AR antagonist (MSX-2), which is stable in aqueous solution, but rapidly cleaved in vivo by phosphatases to release the active compound MSX-2. Intracerebral application of MSX-3 led to a stimulation of motor activity in rats. Catalepsy, induced by pretreatment with either dopamine D1 or D2 antagonist, was potently reversed by intracerebral application of MSX-3. A new A 2A -selective antagonist radioligand, [ 3 H]MSX-2, was prepared, which exhibits a K D value of 8 nM at rat brain striatal membranes.