Numerous pharmacotherapies have been evaluated after experimental traumatic brain injury (TBI). While amantadine (AMT) has shown potential for clinical efficacy, the few studies on its effectiveness have been mixed. It is possible that suboptimal dosing, due to the evaluation of only one dose, may be causing the discrepancies in outcomes. Hence, the goal of the current study was to conduct a dose response of AMT after TBI to determine an optimal behavioral benefit. Anesthetized adult male rats received either a cortical impact of moderate severity or sham injury and then were randomly assigned to receive once daily intraperitoneally injections of AMT (10, 20, or 40 mg/kg) or saline vehicle (VEH, 1 mL/kg) commencing 24 h after injury for 19 days. Motor and cognitive function were assessed on post-operative days 1-5 and 14-19, respectively. There were no statistical differences among the sham groups treated with AMT or VEH so the data were pooled. AMT (20 mg/kg) facilitated beam-balance recovery and spatial learning relative to VEH-treated controls (p < 0.05). No other doses of AMT were effective. These results indicate that dosing should be carefully considered when assessing the effects of pharmacotherapies after TBI so that potential benefits are not inadvertently missed.

Levodopa-induced dyskinesias (LID) appears in more than 50% of Parkinson's disease patients after 5 years of treatment and clinicians always have to ensure that there is a balance between the beneficial effect of the treatment and the potential complications. Areas covered: In this review, the authors discuss the treatment of LID. Treatment can be divided into strategies for preventing their occurrence, modification of dopaminergic therapy, and providing more continuous dopaminergic stimulation as well as the use of nondopaminergic drugs. Expert opinion: Amantadine is currently considered the most effective drug for the treatment of LID. Several compounds developed to target adenosine, adrenergic, glutamatergic, and serotonergic receptors have shown to significantly decrease dyskinesias in animal models. However, despite promising preclinical results, translation to clinical practice remains challenging and majority of these compounds failed to decrease LID in randomized controlled trials with moderate-to-advanced parkinsonian patients. Despite promising results with nondopaminergic drugs, treatment of dyskinesias is still challenging and largely due to their side effects. Future research should focus on developing treatments that can provide continuous dopaminergic delivery throughout the day in a noninvasive manner. Studies on the impact of the early administration of long-acting formulations of levo-3,4-dihydroxy-phenylalanine on dyskinesias are also necessary.

We report the case of an 8-year-old boy who was taking amantadine off label for multiple childhood neurobehavioral disorders and subsequently developed livedo reticularis. Although this side effect is well-described in adult patients taking amantadine for Parkinson disease, it is now being seen in children as the off-label use of amantadine is expanded to this population.