Neuroprotective properties of 5-HT1A receptor agonists in rodent models of focal and global cerebral ischemia.

5-Hydroxytryptamine1A (5-HT1A) receptor agonists have been shown to inhibit the activity of hippocampal, cortical, and dorsal raphé neurons. We tested urapidil and a new 5-HT1A agonist, CM 57493 [4-(3-trifluoromethylphenyl)-1-(2-cyanoethyl)-1,2,3,6-tetrahydropyridine ], for their neuroprotective activity in models of focal and global cerebral ischemia in rodents. After middle cerebral artery-occlusion (MCA-0) in mice, the infarct size was reduced dose dependently by both urapidil and CM 57493. In MCA-occluded rats, CM 57493 (1 and 5 mg/kg) reduced the cortical infarct volume by 30% and application of 10 mg/kg CM 57493 led to a 40% reduction in the cortical infarct volume. The striatal damage could not be influenced by CM 57493 treatment. Furthermore, 1 and 5 mg/kg CM 57493 significantly reduced the neuronal damage within the CA1 sector of the rat hippocampus after 10 min of forebrain ischemia followed by 7 days of recovery. Measurement of cerebral and rectal temperature revealed that the neuroprotective effect of CM 57493 was not caused by a hypothermic effect. We assume that the neuroprotective activity of 5-HT1A agonists is mediated by an inhibitory action on neurons.