The pre-ischaemic neuroprotective potential of a novel polyamine/NMDA antagonist N-1 -dansyl-spermine (1 (.) 5 mg kg (1)) was studied in a transient focal cerebral ischaemia model in mice in comparison to a reference compound, MK-801 (1 or 3 mg kg (1)). The intraluminal suture transient middle cerebral artery occlusion (MCAO) model was used. N-1 -dansyl-spermine and MK-801 were administered (i.p.) 30 min prior to ischaemia. A range of histological and behavioural assessments was employed. N-1 -dansyl-spermine had a comparable effect to MK-801 at reducing the percentage hemisphere lesion volume (%HLV) at the doses tested, Furthermore, N-1-dansyl-spermine reduced the ischaemic brain oedema, which MK-801 did not. N-1-dansyl-spermine significantly reversed the decrease of locomotor activity (LMA) caused by the MCAO and showed a significant effect at improving the rotarod performance impaired by MCAO. In contrast, MK-801 had no beneficial effect on sensorimotor function and even worsened the LMA. These results clearly demonstrate the pre-ischaemic neuroprotective effect of N-1-dansyl-spermine in a transient focal cerebral ischaemia model. (c) 2005 Elsevier B.V. All rights reserved.