Reduction of neurological and EEG consequences of focal brain ischemia in rats by the 5-HT3 receptor antagonist MDL 72222

MDL 72222 is an antagonist at serotonin 5-HT₃ receptors with several pharmacological properties suggesting the potential to favourably modify outcome in focal cerebral ischemia. Conscious Wistar rats underwent occlusion of the left middle cerebral artery (MCAO) by means of intracerebral infusion of solution of the potent vasoconstrictor peptide endothelin-1 (ET1) in a dose of 60 pmol in the vicinity of the artery (model of focal transient cerebral ischemia) in unanesthetized rats. MDL 72222 was injected in a dose of 2 mg/kg intraperitoneally 20 min after ET1. In MDL 72222-treated rats the neurological deficit (postural reflex and limb placing tests) was smaller than in the vehicle-treated rats beginning from day 3 post-ET1 and there-after up to day 14, the neurological scores approached to normal values. Moreover, MDL 72222 eliminated the difference between the neurological scores of the contralateral and ipsilateral to the MCAO body side. In the same rats, electroencephalogram (EEG) was recorded in the forepaw region of the somatosensory cortex (S1FL) at 15 min, 1 h, 4 h, and at day 1, day 3, day 7, and day 14 post-ET1. MDL 72222 eliminated the early EEG power reduction produced by ET1 beginning from 4 h post-ET1 and thereafter up to day 14, the EEG spectral profiles did not differ from those obtained before ET1. These findings are in favour of the suggestion that MDL 72222 may have neuroprotective potential against some functional (neurological and EEG) consequences of the ischemic brain damage.