Ja. Craven et El. Conway, EFFECTS OF ALPHA(2)-ADRENOCEPTOR ANTAGONISTS AND IMIDAZOLINE(2)-RECEPTOR LIGANDS ON NEURONAL DAMAGE IN GLOBAL-ISCHEMIA IN THE RAT, Clinical and experimental pharmacology and physiology, 24(2), 1997, pp. 204-207
1, In the present study the neuroprotective effects of 3 mg/kg idazoxa
n, an alpha(2)-adrenoceptor antagonist and imidazoline(2)-receptor (I-
2-receptor) ligand, 3 mg/kg methoxyidazoxan, a specific alpha(2)-adren
oceptor antagonist, and 0.6 and 3 mg/kg BU224, a selective I-2-recepto
r ligand, were evaluated following 10 min of global ischaemia in rats,
2, Neuronal cell counts in the CA1 region of the hippocampus 8 days p
ostischaemia indicated 46-96% cell loss compared with control(P<0.001)
and a 320% increase in [H-3]-PK11195 binding (P<0.001) used as a mark
er of gliosis, No significant neuroprotective effect could be detected
on these markers of neuronal damage in the active treatment groups. I
n a subset of idazoxan-treated rats, neuronal loss and gliosis was min
imal. 3. Mean body temperature over 3 h postischaemia was lower in ida
zoxan-treated rats than in the other treatment groups (P<0.001) and th
ere 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 m
ethoxyidazoxan are neuroprotective in this ischaemia model and they ra
ise the possibility that any neuroprotective effect of idazoxan may be
related to hypothermic effects of the drug.