This is a sharply focused interdisciplinary, interdepartmental Program Project Grant. All of the proposed research is directed toward in vivo localization of neuro-receptors. Co-investigators include members of our faculty from Pharmacology and Experimental Therapeutics, Neurotoxicology, Neurology, Neurosurgery, Psychiatry, Radiology and Nuclear Medicine (all of The Johns Hopkins Medical Institutions) and the Graduate Chemistry Department of The Johns Hopkins University. The current research is focused on in vivo localization of the dopamine and opiate receptors. Initial research will be directed toward: 1) Rapid """"""""on line"""""""" synthesis of 11C spiroperidol (a dopamine receptor specific binding agent) and 11C diprenorphine (an opiate receptor specific binding agent), and 2) An evaluation of this total system in a variety of animal models, prior to beginning studies in man. Thereafter we will concentrate on studies of those dopamine and opiate receptors in appropriate disease states (including Parkinsonism, Huntington's Disease, Tardive Dyskinesia, Schizophrenia, chronic pain patients, etc.). In addition we will use standardized methods for measurement of regional cerebral blood flow, blood volume and metabolism where indicated in these patients. We believe the ability to study non-invasively such neuroreceptors in man will lead to fundamentally important new information, and provide, in some instances, improved approaches to therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS015080-09
Application #
3099517
Study Section
(SRC)
Project Start
1979-09-01
Project End
1989-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Madar, I; Lesser, R P; Krauss, G et al. (1997) Imaging of delta- and mu-opioid receptors in temporal lobe epilepsy by positron emission tomography. Ann Neurol 41:358-67
Camargo, E E; Szabo, Z; Links, J M et al. (1992) The influence of biological and technical factors on the variability of global and regional brain metabolism of 2-[18F]fluoro-2-deoxy-D-glucose. J Cereb Blood Flow Metab 12:281-90
Dannals, R F; Ravert, H T; Wilson, A A et al. (1990) Synthesis of a selective serotonin uptake inhibitor: [11C]citalopram. Int J Rad Appl Instrum A 41:541-3
Lever, J R; Mazza, S M; Dannals, R F et al. (1990) Facile synthesis of [11C]buprenorphine for positron emission tomographic studies of opioid receptors. Int J Rad Appl Instrum A 41:745-52
Wilson, A A; Dannals, R F; Ravert, H T et al. (1989) Preparation of [11C]- and [125I]IMB: a dopamine D-2 receptor antagonist. Int J Rad Appl Instrum A 40:369-73
Dannals, R F; Langstrom, B; Ravert, H T et al. (1988) Synthesis of radiotracers for studying muscarinic cholinergic receptors in the living human brain using positron emission tomography: [11C]dexetimide and [11C]levetimide. Int J Rad Appl Instrum A 39:291-5
Guilarte, T R; Wagner Jr, H N; Frost, J J (1987) Effects of perinatal vitamin B6 deficiency on dopaminergic neurochemistry. J Neurochem 48:432-9
Ravert, H T; Wilson, A A; Dannals, R F et al. (1987) Radiosynthesis of a selective dopamine D-1 receptor antagonist: R(+)-7-chloro-8-hydroxy-3-[11C]methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3 -benzazepine ([11C]SCH 23390). Int J Rad Appl Instrum A 38:305-6
Guilarte, T R; Wagner Jr, H N (1987) Increased concentrations of 3-hydroxykynurenine in vitamin B6 deficient neonatal rat brain. J Neurochem 49:1918-26
Dannals, R F; Ravert, H T; Wilson, A A et al. (1986) An improved synthesis of (3-N-[11C]methyl)spiperone. Int J Rad Appl Instrum A 37:433-4

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