Biomaterial Database

Ligands for in vivo imaging of nicotinic receptor subtypes in Alzheimer brain. 2000

W Sihver, and B Långström, and A Nordberg

PET-Center/Institute of Chemistry, Uppsala University, Sweden.

The neuronal nicotinic acetylcholine receptors (nAChR) are involved in functional processes in brain including cognitive function and memory. A severe loss of the nAChRs has been detected in brain of patients with Alzheimer's disease (AD). There is a great interest to image nAChRs noninvasive for detection of receptor impairments even at a presymptomatic stage of AD as well for monitoring outcome of drug treatment. (S) [11C]Nicotine, has so far been the only nAChR ligand used in positron emission tomography (PET) studies for visualizing nAChRs in human brain. In order to develop PET/SPECT nAChRs ligands for detection of subtypes of nAChRs nicotine analogues, epibatidine and A-85380 compounds have been characterized in vitro and investigated in vivo. Epibatidine and A-85380 have been found to have higher specific signals and more favorable kinetic parameters than nicotine and its analogues. The epibatidine and A-85380 compounds can also be radiolabeled with high specific radioactivity, show affinities for the nAChRs in the pM range and readily cross the blood-brain barrier. In addition they reversibly bind to the nAChRs and show low non-specific binding and moderately fast metabolism. Due to a probably high alpha4beta2 nAChR selectivity combined with low toxicity, the A-85380 analogs presently seem to be the most promising nAChR ligand imaging of subtypes of nAChRs in human brain.

UI	MeSH Term	Description	Entries
D008024	Ligands	A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)	Ligand
D011323	Primates	An order of mammals consisting of more than 300 species that include LEMURS; LORISIDAE; TARSIERS; MONKEYS; and HOMINIDS. They are characterized by a relatively large brain when compared with other terrestrial mammals, forward-facing eyes, the presence of a CALCARINE SULCUS, and specialized MECHANORECEPTORS in the hands and feet which allow the perception of light touch.	Primate
D011725	Pyridines	Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D011978	Receptors, Nicotinic	One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.	Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D001812	Blood-Brain Barrier	Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.	Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000544	Alzheimer Disease	A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)	Acute Confusional Senile Dementia,Alzheimer's Diseases,Dementia, Alzheimer Type,Dementia, Senile,Presenile Alzheimer Dementia,Senile Dementia, Alzheimer Type,Alzheimer Dementia,Alzheimer Disease, Early Onset,Alzheimer Disease, Late Onset,Alzheimer Sclerosis,Alzheimer Syndrome,Alzheimer Type Senile Dementia,Alzheimer's Disease,Alzheimer's Disease, Focal Onset,Alzheimer-Type Dementia (ATD),Dementia, Presenile,Dementia, Primary Senile Degenerative,Early Onset Alzheimer Disease,Familial Alzheimer Disease (FAD),Focal Onset Alzheimer's Disease,Late Onset Alzheimer Disease,Primary Senile Degenerative Dementia,Senile Dementia, Acute Confusional,Alzheimer Dementias,Alzheimer Disease, Familial (FAD),Alzheimer Diseases,Alzheimer Type Dementia,Alzheimer Type Dementia (ATD),Alzheimers Diseases,Dementia, Alzheimer,Dementia, Alzheimer-Type (ATD),Familial Alzheimer Diseases (FAD),Presenile Dementia,Sclerosis, Alzheimer,Senile Dementia
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001384	Azetidines
D014055	Tomography, Emission-Computed	Tomography using radioactive emissions from injected RADIONUCLIDES and computer ALGORITHMS to reconstruct an image.	CAT Scan, Radionuclide,CT Scan, Radionuclide,Computerized Emission Tomography,Radionuclide Tomography, Computed,Scintigraphy, Computed Tomographic,Tomography, Radionuclide-Computed,Computed Tomographic Scintigraphy,Emission-Computed Tomography,Radionuclide Computer-Assisted Tomography,Radionuclide Computerized Tomography,Radionuclide-Computed Tomography,Radionuclide-Emission Computed Tomography,Tomography, Computerized Emission,CAT Scans, Radionuclide,CT Scans, Radionuclide,Computed Radionuclide Tomography,Computed Tomography, Radionuclide-Emission,Computer-Assisted Tomographies, Radionuclide,Computer-Assisted Tomography, Radionuclide,Computerized Tomography, Radionuclide,Emission Computed Tomography,Emission Tomography, Computerized,Radionuclide CAT Scan,Radionuclide CAT Scans,Radionuclide CT Scan,Radionuclide CT Scans,Radionuclide Computed Tomography,Radionuclide Computer Assisted Tomography,Radionuclide Computer-Assisted Tomographies,Radionuclide Emission Computed Tomography,Scan, Radionuclide CAT,Scan, Radionuclide CT,Scans, Radionuclide CAT,Scans, Radionuclide CT,Tomographic Scintigraphy, Computed,Tomographies, Radionuclide Computer-Assisted,Tomography, Computed Radionuclide,Tomography, Emission Computed,Tomography, Radionuclide Computed,Tomography, Radionuclide Computer-Assisted,Tomography, Radionuclide Computerized,Tomography, Radionuclide-Emission Computed