Biomaterial Database

In Vivo and In Vitro Characteristics of Radiolabeled Vesamicol Analogs as the Vesicular Acetylcholine Transporter Imaging Agents. 2018

Kazuma Ogawa, and Kazuhiro Shiba

Kanazawa University, Graduate School of Pharmaceutical Sciences, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.

The vesicular acetylcholine transporter (VAChT), a presynaptic cholinergic neuron marker, is a potential internal molecular target for the development of an imaging agent for early diagnosis of neurodegenerative disorders with cognitive decline such as Alzheimer's disease (AD). Since vesamicol has been reported to bind to VAChT with high affinity, many vesamicol analogs have been studied as VAChT imaging agents for the diagnosis of cholinergic neurodeficit disorder. However, because many vesamicol analogs, as well as vesamicol, bound to sigma receptors (σ1 and σ2) besides VAChT, almost all the vesamicol analogs have been shown to be unsuitable for clinical trials. In this report, the relationships between the chemical structure and the biological characteristics of these developed vesamicol analogs were investigated, especially the in vitro binding profile and the in vivo regional brain accumulation.

UI	MeSH Term	Description	Entries
D010880	Piperidines	A family of hexahydropyridines.
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
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D050494	Vesicular Acetylcholine Transport Proteins	Vesicular amine transporter proteins that transport the neurotransmitter ACETYLCHOLINE into small SECRETORY VESICLES. Proteins of this family contain 12 transmembrane domains and exchange vesicular PROTONS for cytoplasmic acetylcholine.	Acetylcholine Transporters, Vesicular,Vesicular Acetylcholine Transporter Proteins,VAChT Proteins,Vesicular Acetylcholine Transporter,Acetylcholine Transporter, Vesicular,Transporter, Vesicular Acetylcholine,Transporters, Vesicular Acetylcholine,Vesicular Acetylcholine Transporters
D019275	Radiopharmaceuticals	Compounds that are used in medicine as sources of radiation for radiotherapy and for diagnostic purposes. They have numerous uses in research and industry. (Martindale, The Extra Pharmacopoeia, 30th ed, p1161)	Radiopharmaceutical
D019636	Neurodegenerative Diseases	Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.	Degenerative Diseases, Nervous System,Degenerative Diseases, Central Nervous System,Degenerative Diseases, Neurologic,Degenerative Diseases, Spinal Cord,Degenerative Neurologic Diseases,Degenerative Neurologic Disorders,Nervous System Degenerative Diseases,Neurodegenerative Disorders,Neurologic Degenerative Conditions,Neurologic Degenerative Diseases,Neurologic Diseases, Degenerative,Degenerative Condition, Neurologic,Degenerative Conditions, Neurologic,Degenerative Neurologic Disease,Degenerative Neurologic Disorder,Neurodegenerative Disease,Neurodegenerative Disorder,Neurologic Degenerative Condition,Neurologic Degenerative Disease,Neurologic Disease, Degenerative,Neurologic Disorder, Degenerative,Neurologic Disorders, Degenerative