| Abstract | 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. |
| Authors | J H Prehn, C Backhauss, C Karkoutly, J Nuglisch, B Peruche, C Rossberg, J Krieglstein
(Affiliation: Institut für Pharmakologie und Toxikologie, Fachbereich Pharmazie und Lebensmittelchemie, Marburg, F.R.G.)
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| Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 203
Issue 2
Pg. 213-22
(Oct 15 1991)
ISSN: 0014-2999 NETHERLANDS |
| PMID | 1800118
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Pyridines
- Receptors, Serotonin
- N-Methylaspartate
- Phencyclidine
- CM 57493
|
| Topics |
- Animals
- Body Temperature
(drug effects)
- Brain
(blood supply, drug effects)
- Brain Ischemia
(prevention & control)
- Disease Models, Animal
- Hypothalamus, Posterior
(blood supply, drug effects, pathology)
- Ischemic Attack, Transient
(prevention & control)
- Male
- Mice
- N-Methylaspartate
(antagonists & inhibitors)
- Phencyclidine
(therapeutic use)
- Pyridines
(therapeutic use)
- Rats
- Rats, Inbred Strains
- Receptors, Serotonin
(physiology)
|
