FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2896813194> ?p ?o ?g. }

• W2896813194 abstract "ANAVEX®2-73, a selective sigma-1 receptor (S1R) agonist, has undergone testing in a Phase 2a trial of Alzheimer's disease patients. Over a period of 57 weeks, ANAVEX®2-73 demonstrated a favorable safety profile and a concentration-dependent improvement against exploratory endpoints MMSE and ADCS-ADL. Positron emission tomography (PET) with [18F]FTC-146, a novel S1R radiotracer, was used in the current study to substantiate target engagement in mice. ANAVEX®2-73 was examined using PET and ex vivo autoradiography (ARG) in 7-week-old wild type mice (n=4-5) in 4 dose groups (0, 1, 10, 30 mg/kg PO). 60 minutes after delivery of ANAVEX®2-73, [18F]FTC-146 was injected intravenously (210±22 μCi, 7.77±0.81 MBq) for a 60-minute dynamic PET scan. Subsequently, the mice were perfused and brains were collected for ex vivo ARG. Using an image-derived arterial input function from the left ventricle of the heart, two-tissue compartment kinetic modeling (PMOD 3.7) was performed to determine the binding potential for receptor occupancy for whole mouse brains. Separate mice (n=6, 0 mg/kg ANAVEX®2-73) were used to derive whole blood to plasma ratios and parent fractions for metabolism correction at times 1, 5, 15, 30, and 60 minutes. For radiometabolite studies, [18F]FTC-146 was injected intravenously (780±214 μCi, 28.86±7.92 MBq). PET data show S1R occupancy is dose-dependent for ANAVEX®2-73 with an apparent plateau of approximately 60% in whole brain. For analysis of ex vivo ARG, selected brain regions (frontal cortex, caudate, hippocampus, thalamus, amygdala, pons, cerebellum) were analyzed and receptor occupancy ranged from 30-60%. These results were compared with PRE-084, a S1R literature standard. This is the first imaging study of ANAVEX®2-73 and the results confirm dose-dependent S1R target engagement via ex vivo ARG and PET using [18F]FTC-146 as the radiotracer. The range of doses employed here (1-30 mg/kg PO) have been used in numerous animal disease models with improvements observed in both behavioral and biochemical readouts. Since the mice equivalent human plasma exposures correspond to human doses of 10-50 mg PO, which have been assessed in ANAVEX®2-73 clinical studies, these results pose the possibility that S1R receptor occupancy in humans is similar to that found in mice . A) Whole brain time activity curves calculated using 2-tissue compartment modeling (n=1/dose group ). B) Receptor occupancy calculated using binding potential values (n=4-5 per dose group)." @default.
• W2896813194 created "2018-10-26" @default.
• W2896813194 creator A5006944910 @default.
• W2896813194 creator A5014228486 @default.
• W2896813194 creator A5022357912 @default.
• W2896813194 creator A5025054177 @default.
• W2896813194 creator A5028646315 @default.
• W2896813194 creator A5029901905 @default.
• W2896813194 creator A5056898095 @default.
• W2896813194 creator A5074090472 @default.
• W2896813194 creator A5087461202 @default.
• W2896813194 creator A5090143681 @default.
• W2896813194 date "2018-07-01" @default.
• W2896813194 modified "2023-10-16" @default.
• W2896813194 title "P4‐262: SIGMA‐1 RECEPTOR TARGET OCCUPANCY STUDY WITH DYNAMIC PET SCAN ANALYSIS OF ANAVEX ^® 2‐73: A CLINICAL CANDIDATE FOR NEURODEGENERATIVE AND NEURODEVELOPMENTAL DISEASES" @default.
• W2896813194 doi "https://doi.org/10.1016/j.jalz.2018.07.084" @default.
• W2896813194 hasPublicationYear "2018" @default.
• W2896813194 type Work @default.
• W2896813194 sameAs 2896813194 @default.
• W2896813194 citedByCount "0" @default.
• W2896813194 crossrefType "journal-article" @default.
• W2896813194 hasAuthorship W2896813194A5006944910 @default.
• W2896813194 hasAuthorship W2896813194A5014228486 @default.
• W2896813194 hasAuthorship W2896813194A5022357912 @default.
• W2896813194 hasAuthorship W2896813194A5025054177 @default.
• W2896813194 hasAuthorship W2896813194A5028646315 @default.
• W2896813194 hasAuthorship W2896813194A5029901905 @default.
• W2896813194 hasAuthorship W2896813194A5056898095 @default.
• W2896813194 hasAuthorship W2896813194A5074090472 @default.
• W2896813194 hasAuthorship W2896813194A5087461202 @default.
• W2896813194 hasAuthorship W2896813194A5090143681 @default.
• W2896813194 hasConcept C126322002 @default.
• W2896813194 hasConcept C150903083 @default.
• W2896813194 hasConcept C170493617 @default.
• W2896813194 hasConcept C185592680 @default.
• W2896813194 hasConcept C207001950 @default.
• W2896813194 hasConcept C26291073 @default.
• W2896813194 hasConcept C2775842073 @default.
• W2896813194 hasConcept C2777415128 @default.
• W2896813194 hasConcept C2778921608 @default.
• W2896813194 hasConcept C2778938600 @default.
• W2896813194 hasConcept C2989005 @default.
• W2896813194 hasConcept C71924100 @default.
• W2896813194 hasConcept C86803240 @default.
• W2896813194 hasConceptScore W2896813194C126322002 @default.
• W2896813194 hasConceptScore W2896813194C150903083 @default.
• W2896813194 hasConceptScore W2896813194C170493617 @default.
• W2896813194 hasConceptScore W2896813194C185592680 @default.
• W2896813194 hasConceptScore W2896813194C207001950 @default.
• W2896813194 hasConceptScore W2896813194C26291073 @default.
• W2896813194 hasConceptScore W2896813194C2775842073 @default.
• W2896813194 hasConceptScore W2896813194C2777415128 @default.
• W2896813194 hasConceptScore W2896813194C2778921608 @default.
• W2896813194 hasConceptScore W2896813194C2778938600 @default.
• W2896813194 hasConceptScore W2896813194C2989005 @default.
• W2896813194 hasConceptScore W2896813194C71924100 @default.
• W2896813194 hasConceptScore W2896813194C86803240 @default.
• W2896813194 hasIssue "7S_Part_29" @default.
• W2896813194 hasLocation W28968131941 @default.
• W2896813194 hasOpenAccess W2896813194 @default.
• W2896813194 hasPrimaryLocation W28968131941 @default.
• W2896813194 hasRelatedWork W1796991209 @default.
• W2896813194 hasRelatedWork W1981051488 @default.
• W2896813194 hasRelatedWork W2051166648 @default.
• W2896813194 hasRelatedWork W2083210814 @default.
• W2896813194 hasRelatedWork W2117290479 @default.
• W2896813194 hasRelatedWork W2169571869 @default.
• W2896813194 hasRelatedWork W2170524884 @default.
• W2896813194 hasRelatedWork W2182920042 @default.
• W2896813194 hasRelatedWork W2567080316 @default.
• W2896813194 hasRelatedWork W3194480446 @default.
• W2896813194 hasVolume "14" @default.
• W2896813194 isParatext "false" @default.
• W2896813194 isRetracted "false" @default.
• W2896813194 magId "2896813194" @default.
• W2896813194 workType "article" @default.