Is the 5-HT2C receptor a therapeutic target in cerebral ischaemia?

This study examines the effect of a 5-HT2C agonist (RO 60-0175, (s)-2-(chloro-5-fluoro-indol-1-yl)-1-methylethylamine) and a 5-HT2C antagonist (RO 43-0440, benzofuran-2-carboxamidine) for neuroprotective activity in a rat model of global cerebral ischaemia. A mini-osmotic pump implanted subcutaneously delivered 0.25 mg/kg/hr. Seven days after ischaemia the rats were sacrificed and the damage in the CA1 pyramidal cell layer in hippocampus was estimated and the treated groups were compared with vehicle groups. Pretreatment with the 5-HT2C agonist RO 60-0175 significantly increased the damage, whereas the 5-HT2C antagonist RO 43-0440 had no effect on the cell damage. Measurement of the core temperature in a RO 60-0175-treated group of rats revealed no effect compared to a vehicle-treated group. Thus the aggravation of damage in the RO 60-0175-treated group cannot be explained by temperature effect. Our data do not indicate the 5-HT2C receptor as a therapeutic target in cerebral ischaemia.