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A new human (psycho)pharmacology tool: the multiple organs coincidences counter (MOCC)

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS, Psychopharmacology Unit, University of Bristol, Bristol BS8 1TD, UK

G. Forse

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS

A. Haida

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS

R. Gunn

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS

J. Melichar

Psychopharmacology Unit, University of Bristol, Bristol BS8 1TD, UK

K. Poole

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS

D. Bateman

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS

D. Fahy

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS

L. Schnorr

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS

D. Brown

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS

C. Rhodes

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS

D.J. Nutt

Psychopharmacology Unit, University of Bristol, Bristol BS8 1TD, UK

T. Jones

Methodology and Neuroscience Sections, MRC Cyclotron Unit, Hammersmith Hospital, London W12 0HS

We describe a novel instrument which is capable of measuring the uptake of radioligand in human organs in vivo with the administration of very small doses of positron-emitting radioligands. This technique readily detects the displacement or reduced uptake of radioligand when a competitive agonist or antagonist is administered. This system provides no tomographic information, but the small radioactive doses involved mean that investigations can be repeated at regular intervals and that female volunteers can also participate. We administered [¹¹ C]flumazenil, [¹¹C]diprenorphine, [¹¹C]meta -hydroxyephedrine (MHED) and [¹¹C]RTI 55 to healthy male volunteers and performed control, pre-loading and displacement experiments. These demonstrate the feasibility of using this technique to investigate benzodiazepine and opiate receptor occupancy, as well as occupancy at dopamine, noradrenaline and serotonin (5-HT) re-uptake sites. This method is likely to be useful in pharmacokinetic/pharmacodynamic experiments, in drug development and discovery and in the development of novel imaging radioligands.

Key Words: positron emission • pharmacokinetic • benzodiazepine receptor • opioid receptor • noradrenaline re- uptake site • serotonin re-uptake site • dopamine re-uptake site • drug development and discovery • radioligand

Journal of Psychopharmacology, Vol. 9, No. 4, 294-306 (1995)
DOI: 10.1177/026988119500900402


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