The neuroprotective effects of intravenous rasagiline were investigated in a rat model of stroke. Middle cerebral artery (MCA) occlusion was performed in male rats and the short- (neurological severity score [NSS], infarct size), intermediate- (cognition) and long-term (necrotic area) effects were assessed. A bolus (3 mg/kg) of rasagiline followed by a 3-h infusion (3 mg/kg/h), initiated immediately after MCA occlusion, reduced infarct size by 48.6% and NSS by 32.7% relative to saline treatment. Cognitive function, tested in a water maze 2-3 weeks after occlusion, also significantly improved compared with saline-treated controls. Necrotic brain area was 35-50% smaller with rasagiline than with saline following a single bolus dose. The single bolus rasagiline dose was as effective as a rasagiline bolus followed by rasagiline infusion in short-term outcomes. The neuroprotective effect of rasagiline was fully reproducible when administered at 2 h following occlusion but not after 4 h.
This study investigated whether rasagiline and selegiline (MAO-B inhibitors) induce serotonin syndrome in fluoxetine-treated rats. Rats received rasagiline (0.1, 0.5, 2.0 mg/kg), or selegiline (0.8, 4.0, 16.0 mg/kg) (doses reflecting the clinical ratio of 1:8 base) in drinking water for 28 days. During the last 21 days, they received injections of fluoxetine 10 mg/kg (controls received water only, then saline injections; a fluoxetine only group received water only then fluoxetine). Serotonin syndrome was assessed using neurological severity score (NSS), food intake and weight gain. Mean NSS significantly increased, and weight and food consumption significantly decreased in rats receiving fluoxetine alone compared with controls. Selegiline 16 mg/kg but not rasagiline (regardless of dose) exacerbated these effects. We concluded that selegiline's amphetamine-like metabolites may increase synaptic cathecholamines and possibly serotonin, aggravating fluoxetine's effect. Rasagiline is devoid of this effect and may therefore be safer for use with serotonergic drugs in parkinsonian patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.