Epibatidine analogues have been labelled with I-123 for single photon emission computed tomography and with short half-life positron emitters (C-11 and F-18) for PET. For easier radiopharmacological studies the bromo analogue of epibatidine (norchlorobromoepibatidine or exo-7-azabicyclo-2-(2-bromo-5-pyridyl)-[2.2.1]heptane) was labelled with Br-76, a longer half-life positron emitter, (T1/2 = 16.2h). [76Br]-norchlorobromoepibatidine was prepared by using a Cu+ assisted bromodeiodination exchange from the iodo analogue in reducing conditions at 190 degrees C. The tracer purified by RP-HPLC was obtained in 70% radiochemical yield with a specific radioactivity of 20 GBq/micromol. Radiochemical and chemical purities measured by radio-TLC and HPLC were >98%.
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Evaluation of novel epibatidine analogs in the rat nicotine drug discrimination assay and in the rat chronic constriction injury neuropathic pain model.
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Nicotine is the primary psychoactive component responsible for maintaining tobacco dependence in humans. Chronic pain is often a consequence of tobacco-related pathologies, and the development of a dual therapeutic that could treat chronic pain and tobacco dependence would be advantageous. Epibatidine reliably substitutes for nicotine in the drug discrimination assay, and is a potent analgesic, but has a side-effect profile that limits its therapeutic potential.
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