Effects of alpha 2-adrenoceptor antagonists and imidazoline2-receptor ligands on neuronal damage in global ischaemia in the rat.
1. In the present study the neuroprotective effects of 3 mg/kg idazoxan, an alpha 2-adrenoceptor antagonist and imidazoline2-receptor (I2-receptor) ligand, 3 mg/kg methoxyidazoxan, a specific alpha 2-adrenoceptor antagonist, and 0.6 and 3 mg/kg BU224, a selective I2-receptor ligand, were evaluated following 10 min of global ischaemia in rats. 2. Neuronal cell counts in the CA1 region of the hippocampus 8 days postischaemia indicated 46-96% cell loss compared with control (P < 0.001) and a 320% increase in [3H]-PK11195 binding (P < 0.001) used as a marker of gliosis. No significant neuroprotective effect could be detected on these markers of neuronal damage in the active treatment groups. In a subset of idazoxan-treated rats, neuronal loss and gliosis was minimal. 3. Mean body temperature over 3 h postischaemia was lower in idazoxan-treated rats than in the other treatment groups (P < 0.001) and there was a correlation between mean body temperature and cell counts (P < 0.01) and mean body temperature and gliosis in this group (P = 0.057). 4. These results indicate that at the doses used neither BU224 nor methoxyidazoxan are neuroprotective in this ischaemia model and they raise the possibility that any neuroprotective effect of idazoxan may be related to hypothermic effects of the drug.
Craven
J A
JA
University of Melbourne, Department of Medicine, Austin & Repatriation Medical Centre, Heidelberg, Victoria, Australia.
Conway
E L
EL
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism* / Q000494:pharmacology*; D054755:Imidazoline Receptors; D008024:Ligands; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000378:metabolism*
D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; C105826:BU 224; D007093:Imidazoles; D054755:Imidazoline Receptors; D008024:Ligands; D011955:Receptors, Drug; C058525:2-methoxyidazoxan; D019329:Idazoxan