Molecular Psychiatry (2011) 16, 785; doi:10.1038/mp.2011.83

Molecular and functional neuroimaging of human opioid receptor pharmacology

E A Rabiner1,2, J Beaver1, A Makwana1, G Searle1, C Long1, P J Nathan3,4, R D Newbould1, J Howard1, S R Miller5, M A Bush6, S Hill1, R Reiley1, J Passchier1, R N Gunn1,2,7, P M Matthews1,2 and E T Bullmore3,4

  1. 1GSK Clinical Imaging Centre, Imperial College London, Hammersmith Hospital, London, UK
  2. 2Centre for Neurosciences, Division of Experimental Medicine and Toxicology, Imperial College, London, UK
  3. 3GSK Academic Discovery Performance Unit and Clinical Unit Cambridge, Addenbrooke's Centre for Clinical Investigations, Cambridge Biomedical Campus, Cambridge, UK
  4. 4Department of Psychiatry, Behavioural & Clinical Neuroscience Institute, University of Cambridge, UK
  5. 5GSK Quantitative Sciences, Stevenage, UK
  6. 6GSK Clinical Pharmacology Modeling and Simulation, NC, USA
  7. 7Department of Engineering Science, University of Oxford, Oxford, UK

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The effects of GSK1521498, a new μ-opioid receptor antagonist, were imaged in the human brain using a combination of positron emission tomography and functional magnetic resonance imaging. (a) The occupancy of μ-opioid receptors by [11C]carfentanil, a radioligand for the opioid receptor, was measured with positron emission tomography at baseline and following the administration of GSK1521498 (50mg). Compared with baseline, GSK1521498 significantly reduces radioligand binding, indicating that it has high affinity for the target in the human brain. (b) Brain activation by a palatable food stimulus was measured with functional magnetic resonance imaging after oral administration of GSK1521498 or naltrexone, another opioid antagonist. Yellow voxels show brain areas where GSK1521498 had significantly greater effects than naltrexone in attenuating reward-related activation; green voxels show areas where naltrexone had a greater effect than GSK1521498. z indicates the distance (mm), superior or inferior, to the intercommissural plane in standard stereotactic space. These results indicate that the pharmacodynamics of GSK1521498 can be measured, and differentiated from naltrexone, using functional magnetic resonance imaging. For more info on this topic, please refer to the article by Rabiner et al. on pages 826–835.