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Synthesis and Evaluation of Compound Targeting α7 and ß2 Subunits in Nicotinic Acetylcholinergic Receptor.
Singh, Karanveer; Ngo, Allyson; Keerthisinghe, Oshini V; Patel, Krystal K; Liang, Christopher; Mukherjee, Jogeshwar.
Afiliación
  • Singh K; Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA.
  • Ngo A; Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA.
  • Keerthisinghe OV; Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA.
  • Patel KK; Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA.
  • Liang C; Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA.
  • Mukherjee J; Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA.
Molecules ; 28(24)2023 Dec 16.
Article en En | MEDLINE | ID: mdl-38138615
ABSTRACT
Nicotinic acetylcholine receptors (nAChRs) are involved in various central nervous system functions and have also been implicated in several neurodegenerative disorders. The heteromeric α4ß2* and homomeric α7 are two major nAChR subtypes which have been studied in the brain using positron emission tomography (PET). Our comparative autoradiographic studies of the two receptor types in the mouse and rat brains show major differences in the thalamus (α4ß2* >> α7), hippocampus (α7 >> α4ß2*), and subiculum (α4ß2* >> α7). A relatively newer heteromeric α7ß2 nAChR subtype has been identified in the brain which may have a greater role in neurodegeneration. We report the development of KS7 (3-(2-(S)-azetidinylmethoxy)-5-(1,4-diaza-bicyclo[3.2.2]nonane)pyridine) which incorporates structural features of Nifzetidine (high affinity for α4ß2* nAChR) and ASEM (high affinity for α7 nAChR) in an effort to target α7 and ß2 subunits in α7ß2 nAChR. KS7 exhibited higher affinities (IC50 = 50 to 172 nM) for [3H]cytisine radiolabeled sites and weaker affinities (IC50 = 10 µM) for [125I]-α-bungarotoxin radiolabeled rat brain sites in several brain regions. The weaker affinity of KS7 to α7 nAChR may suggest lack of binding at the α7 subunit of α7ß2 nAChR. A radiolabeled derivative of KS7 may be required to identify any specific binding to brain regions suggested to contain α7ß2 nAChR.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Nicotínicos Límite: Animals Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores Nicotínicos Límite: Animals Idioma: En Revista: Molecules Asunto de la revista: BIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza