-(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia.
[(S)-Alpha-phenyl-2-pyridine-ethanamine dihydrochloride] (ARL 15896AR) is a low affinity uncompetitive N-methyl-D-aspartic acid receptor antagonist that was tested in animal models of anoxia and ischemia. Pretreatment of rodents with ARL 15896AR extended survival time during exposure to hypoxia. Wit...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
1997
|
| _version_ | 1797081798177456128 |
|---|---|
| author | Cregan, E Peeling, J Corbett, D Buchan, A Saunders, J Auer, R Gao, M Mccarthy, D Eisman, MS Campbell, T Murray, R Stagnitto, M Palmer, G |
| author_facet | Cregan, E Peeling, J Corbett, D Buchan, A Saunders, J Auer, R Gao, M Mccarthy, D Eisman, MS Campbell, T Murray, R Stagnitto, M Palmer, G |
| author_sort | Cregan, E |
| collection | OXFORD |
| description | [(S)-Alpha-phenyl-2-pyridine-ethanamine dihydrochloride] (ARL 15896AR) is a low affinity uncompetitive N-methyl-D-aspartic acid receptor antagonist that was tested in animal models of anoxia and ischemia. Pretreatment of rodents with ARL 15896AR extended survival time during exposure to hypoxia. With the rat four-vessel occlusion model of global ischemia (20 min), oral dosing commencing at reflow, resulted in significant protection of the CA1 hippocampal neurons. ARL 15896AR was, however, ineffective in the rat two-vessel occlusion model and in the gerbil models of forebrain ischemia, the latter due to an inability to attain suitable plasma levels. In the spontaneously hypertensive rat model of middle cerebral artery occlusion (MCAO) (2 hr plus 22 hr reflow), acute dosing with ARL 15896AR (i.p.) beginning from 30 min before or up to 1 hr post-MCAO significantly reduced cortical infarct volume. The ability of ARL 15896AR to influence infarct size, as well as functional correlates was examined in SHR after 90 min of MCAO. T2 weighted magnetic resonance images taken at 2 and 6 days post-MCAO revealed significantly smaller lesion sizes in the group receiving injections with ARL 15896AR beginning 30 min after occlusion. Spontaneously hypertensive rats were subsequently tested (30-42 days post-MCAO) and found to be deficient in skilled use of the forepaws (staircase test). The contralateral forepaw was most severely impaired, however, ARL 15896AR treatment prevented motor impairment in only the ipsilateral forepaw. Histopathological examination of cortical infarct size was unremarkable between treated and control rats. The findings indicate that ARL 15896AR exhibits neuroprotection in global and focal models of ischemia |
| first_indexed | 2024-03-07T01:19:06Z |
| format | Journal article |
| id | oxford-uuid:8fba8a08-1088-4363-aff5-5418687e48f8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:19:06Z |
| publishDate | 1997 |
| record_format | dspace |
| spelling | oxford-uuid:8fba8a08-1088-4363-aff5-5418687e48f82022-03-26T23:06:33Z-(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8fba8a08-1088-4363-aff5-5418687e48f8EnglishSymplectic Elements at Oxford1997Cregan, EPeeling, JCorbett, DBuchan, ASaunders, JAuer, RGao, MMccarthy, DEisman, MSCampbell, TMurray, RStagnitto, MPalmer, G[(S)-Alpha-phenyl-2-pyridine-ethanamine dihydrochloride] (ARL 15896AR) is a low affinity uncompetitive N-methyl-D-aspartic acid receptor antagonist that was tested in animal models of anoxia and ischemia. Pretreatment of rodents with ARL 15896AR extended survival time during exposure to hypoxia. With the rat four-vessel occlusion model of global ischemia (20 min), oral dosing commencing at reflow, resulted in significant protection of the CA1 hippocampal neurons. ARL 15896AR was, however, ineffective in the rat two-vessel occlusion model and in the gerbil models of forebrain ischemia, the latter due to an inability to attain suitable plasma levels. In the spontaneously hypertensive rat model of middle cerebral artery occlusion (MCAO) (2 hr plus 22 hr reflow), acute dosing with ARL 15896AR (i.p.) beginning from 30 min before or up to 1 hr post-MCAO significantly reduced cortical infarct volume. The ability of ARL 15896AR to influence infarct size, as well as functional correlates was examined in SHR after 90 min of MCAO. T2 weighted magnetic resonance images taken at 2 and 6 days post-MCAO revealed significantly smaller lesion sizes in the group receiving injections with ARL 15896AR beginning 30 min after occlusion. Spontaneously hypertensive rats were subsequently tested (30-42 days post-MCAO) and found to be deficient in skilled use of the forepaws (staircase test). The contralateral forepaw was most severely impaired, however, ARL 15896AR treatment prevented motor impairment in only the ipsilateral forepaw. Histopathological examination of cortical infarct size was unremarkable between treated and control rats. The findings indicate that ARL 15896AR exhibits neuroprotection in global and focal models of ischemia |
| spellingShingle | Cregan, E Peeling, J Corbett, D Buchan, A Saunders, J Auer, R Gao, M Mccarthy, D Eisman, MS Campbell, T Murray, R Stagnitto, M Palmer, G -(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia. |
| title | -(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia. |
| title_full | -(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia. |
| title_fullStr | -(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia. |
| title_full_unstemmed | -(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia. |
| title_short | -(S)-Alpha-phenyl-2-pyridine-ethanamine Dihydrochloride-, a low affinity uncompetitive N-methyl-D-aspartic acid antagonist, is effective in rodent models of global and focal ischemia. |
| title_sort | s alpha phenyl 2 pyridine ethanamine dihydrochloride a low affinity uncompetitive n methyl d aspartic acid antagonist is effective in rodent models of global and focal ischemia |
| work_keys_str_mv | AT cregane salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT peelingj salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT corbettd salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT buchana salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT saundersj salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT auerr salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT gaom salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT mccarthyd salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT eismanms salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT campbellt salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT murrayr salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT stagnittom salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia AT palmerg salphaphenyl2pyridineethanaminedihydrochloridealowaffinityuncompetitivenmethyldasparticacidantagonistiseffectiveinrodentmodelsofglobalandfocalischemia |