5-hydroxytryptamine1A agonists. A new therapeutic principle for stroke treatment.
We conducted the present study to investigate the effects of 5-hydroxytryptamine agonists on brain morphology after the induction of focal cerebral ischemia by permanent occlusion of the left middle cerebral artery in rats and mice. Forty-eight hours after vessel occlusion, the damage was quantified in rats by planimetry and subsequent integration on cresyl violet-stained serial sections and in mice by planimetric analysis of the damaged cortical surface after counterstaining with carbon black. All 5-HT1A agonists investigated substantially decreased cortical infarct size in the rat focal ischemia model (p less than 0.05). Drugs were applied 30 minutes before the induction of ischemia, and efficacy was demonstrated for 8-OH-DPAT (1 mg/kg s.c.), buspirone (10 mg/kg i.p.), gepirone (10 mg/kg i.p.), ipsapirone (10 or 30 mg/kg i.p.), and Bay R 1531 (1 mg/kg i.p.). The most pronounced effects were seen with the higher dose of ipsapirone and Bay R 1531, both compounds reducing cortical infarct size by more than 60%. Except for 8-OH-DPAT, the 5-HT1A agonists also caused a reduction in total infarct volumes. In a separate series, ipsapirone (30 mg/kg i.p.), applied 1 hour after vessel occlusion, led to a reduction in cortical and total infarct volumes by about 50% compared with corresponding controls (p less than 0.05). In neither series was striatal damage influenced. We tested the compounds in the mouse ischemia model over a broad dose range.(ABSTRACT TRUNCATED AT 250 WORDS)