Galantamine: Difference between revisions

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===Mechanism of Action===

<scene name='Galantamine/Ache/1'>TextToBeDisplayed</scene>

Described above, <scene name='1w4l/Al/1'>Galantamine</scene> (abbreviated as <scene name='1w4l/Al/2'>GAL</scene>; colored red) is a CAS-binding inhibitor and it is currently used in therapy of the AD. Conjugate of GAL through the <scene name='1w4l/Al/3'>alkyl linker</scene> (8 carbons, yellow) with a <scene name='1w4l/Al/4'>phthalimido moiety</scene> (blueviolet) called '''compound 3''' has a larger affinity for AChE than that of GAL alone. This is similar to previously described cases of bivalent ligands (''e.g.'' '''(''RS'')-(±)-tacrine-(10)-hupyridone'''). A comparison between <scene name='1w4l/Comparison/1'>compound 3</scene>/''Tc''AChE ([[1w4l]]) and <scene name='1w4l/Comparison/2'>galanthamine/TcAChE</scene> structure ([[1dx6]]) shows an identical binding mode of the GAL-moiety (transparent red) of '''compound 3''' to that of GAL alone (blue) at the CAS. A PEG molecule (gray) is located at the active site of the galanthamine/''Tc''AChE structure. The alkyl linker spans the active-site gorge and the phthalimido moiety of '''compound 3''' is situated near Trp279 at the PAS. '''Compound 3''' has higher affinity to ''Tc''AChE than GAL. This can be explained by the higher number of interactions between '''compound 3''' (which interacts not only with residues within CAS but also within PAS) and ''Tc''AChE relative to GAL <ref name="Guillou">PMID:15563167</ref>.

===Pharmacokinetics===

Galantamine: Difference between revisions

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@@ Line 11: / Line 11: @@
 ===Mechanism of Action===
 <scene name='Galantamine/Ache/1'>TextToBeDisplayed</scene>
+Described above, <scene name='1w4l/Al/1'>Galantamine</scene> (abbreviated as <scene name='1w4l/Al/2'>GAL</scene>; <font color='red'><b>colored red</b></font>) is a CAS-binding inhibitor and it is currently used in therapy of the AD. Conjugate of GAL through the <scene name='1w4l/Al/3'>alkyl linker</scene> (8 carbons, <font color='black'><b>yellow</b></font>) with a <scene name='1w4l/Al/4'>phthalimido moiety</scene> <font color='blueviolet'><b>(blueviolet)</b></font> called '''compound 3''' has a larger affinity for AChE than that of GAL alone. This is similar to previously described cases of bivalent ligands (''e.g.'' '''(''RS'')-(±)-tacrine-(10)-hupyridone'''). A comparison between <scene name='1w4l/Comparison/1'>compound 3</scene>/''Tc''AChE ([[1w4l]]) and <scene name='1w4l/Comparison/2'>galanthamine/TcAChE</scene> structure ([[1dx6]]) shows an identical binding mode of the <font color='red'><b>GAL-moiety (transparent red)</b></font> of '''compound 3''' to that of <font color='blue'><b>GAL alone (blue)</b></font> at the CAS. A <font color='gray'><b>PEG molecule (gray)</b></font> is located at the active site of the galanthamine/''Tc''AChE structure. The alkyl linker spans the active-site gorge and the phthalimido moiety of '''compound 3''' is situated near Trp279 at the PAS.  '''Compound 3''' has  higher affinity to ''Tc''AChE than GAL. This can be explained by the higher number of interactions between '''compound 3''' (which interacts not only with residues within CAS but also within PAS) and ''Tc''AChE relative to GAL <ref name="Guillou">PMID:15563167</ref>.
 ===Pharmacokinetics===