@article{Azim_Kozaka_Uno_Miwa_Kitamura_Ogawa_Shiba_2016, title={Syntheses and In-vitro Evaluation of Tetrahydroaminoacridine (THA) Based Analogues as High Affinity Choline Transporter (HAChT) Imaging Probe}, volume={17}, url={https://banglajol.info/index.php/BJNM/article/view/28192}, DOI={10.3329/bjnm.v17i2.28192}, abstractNote={<p>Introduction: In cholinergic neurons, high affinity choline uptake (HACU) by the high affinity choline transporter (HAChT) is a rate-limiting and regulatory step for the synthesis of Acetylcholine (Ach).Thus, HAChT appear to be a relatively specific presynaptic marker for cholinergic neurons in Alzheimer’s disease.</p><p>Objectives: The principle objective of the study is to check the affinity of tetrahydroaminoacridine (THA) derivatives for HAChT. Another objective of the research work is to clarify whether the hemicholinium-3 (ChT inhibitor) and HACU enhancer molecules share the same binding sites or not.</p><p>Materials and Methods: The inhibition activities of tacrine, the 2,3-dimethylfuran derivative of tacrine (DMTA) and their corresponding 2-oxo-1-pyrrolidineacetyl derivatives, namely PTAA and MKC-231 were measured by displacement of a typical HAChT antagonist [<sup>3</sup>H]HC-3 in rat cerebral membrane. The percentage of inhibition against the binding of [<sup>3</sup>H]HC-3 to HAChT were calculated using GraphPad Prism v4 software.</p><p>Results: Hemicholinium-3 showed affinity for HAChT (IC<sub>50</sub> = 20 nM) in the in vitro binding assay. A very insignificant inhibition activity (IC<sub>50</sub> = 1000 nM) of Tacrine was revealed. The newly synthesized tacrine derivatives, DMTA and PTAA did not show any affinity for HAChT. Although MKC-231 was reported to enhance cholinergic activity at synaptic terminals, it did not show any affinity for the HAChT in [<sup>3</sup>H]HC-3 binding assay.</p><p>Conclusion: In vitro [<sup>3</sup>H]HC-3 binding assay revealed no affinity of MKC-231, tacrine and its corresponding2-oxo-1-pyrrolidineacetate derivative towards HAChT. So, it is worthy to develop radiolabeled HC-3 derivatives with high affinity for HAChT, which can diffuse the BBB, to enable the in vivo investigation of HACU system.</p><p>Bangladesh J. Nuclear Med. 17(2): 97-102, July 2014</p>}, number={2}, journal={Bangladesh Journal of Nuclear Medicine}, author={Azim, Mohammad Anwar Ul and Kozaka, Takashi and Uno, Izumi and Miwa, Daisuke and Kitamura, Yoji and Ogawa, Kazuma and Shiba, Kahuhiro}, year={2016}, month={Jun.}, pages={97–102} }