Lacosamide, epilepsy drug, shows neuroprotective effects in rat model

More dopaminergic neurons, better motor function seen in treated animals

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Lacosamide, a medication approved to treat epilepsy, showed a potential to be neuroprotective in a rat model of Parkinson’s disease, a study reports.

Treatment with lacosamide significantly prevented the loss of dopamine-producing neurons that marks Parkinson’s, boosted dopamine production in key areas of the brain, and improved motor function in these animals.

Study findings “provide encouraging evidence for the prospective use of lacosamide, a drug often prescribed to treat adult and adolescent epilepsy, as a novel Parkinson’s disease therapeutic agent,” the researchers wrote.

The study, “Lacosamide Exhibits Neuroprotective Effects in a Rat Model of Parkinson’s Disease,” was published in the Journal of Chemical Neuroanatomy

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A neurodegenerative disease, Parkinson’s is primarily marked by motor symptoms, such as tremors and walking difficulties. These symptoms arise due to the death of dopamine-producing nerve cells in the substantia nigra, a brain region that regulates muscle movement and coordination. Dopamine is a brain chemical messenger essential for muscle control.

Current treatments, including its mainstay levodopa, a precursor to dopamine, help to ease symptoms.

Lacosamide, sold as Vimpat among other names, is approved as an add-on or standalone epilepsy treatment. It works in two ways to help control seizures. First, it slows the process that inactivates sodium channels in the brain, helping to reduce the chances of a seizure. Second, it affects a protein called collapsin response mediator protein 2, also helping in seizure control.

Likewise, “lacosamide exhibits anti-inflammatory and antioxidant properties, which are crucial in neurodegenerative processes,” and it “has shown potential in preserving mitochondrial function,” the researchers noted. Mitochondria are a cell’s energy source

In previous studies, lacosamide also demonstrated a significant ability to reduce tremors in rats, and its antitremor effect was found to be similar to or stronger than known antitremor medications.

No studies to date, however, have assessed its potential in Parkinson’s disease.

Lacosamide’s use appears to support motor function in the rat model

Researchers in Turkey examined the therapeutic effects of lacosamide in a rat model of Parkinson’s. The model was generated by exposing the rats to the pesticide rotenone, which induces some motor and biochemical changes similar to those in patients.

Rats were placed equally across three groups: one was given a solution without rotenone to serve as healthy controls, while groups two and three received rotenone for 10 days.

Motor function in all 21 rats then was assessed using the apomorphine rotation test. Apomorphine makes the animals start to rotate or turn in circles, because the drug affects certain parts of the brain responsible for movement. Researchers observed how many times the animals turned or rotated for 10 minutes, with the rate of turns increasing as the disease progresses.

Over the next 28 days, group two was given a saline solution, while group three was treated with lacosamide. Another round of apomorphine-induced rotation tests were performed to assess treatment effects on motor function.

As expected, the number of rotations was significantly higher in rats with rotenone-induced Parkinson’s features compared with healthy controls, a mean of 128.3 vs. 1.3 turns over 10 minutes. However, rats treated with lacosamide showed a significant decrease in the number of rotations relative to the disease model group left untreated: a mean 61.2 vs. 158.4 turns in 10 minutes.

Researchers then analyzed the brain’s nigrostriatal dopaminergic pathway — which includes the substantia nigra and the striatum, two areas marked by the loss of dopamine-producing neurons during the early stages of Parkinson’s.

More dopamine-producing neurons evident in brains of treated animals

A decrease in the overall number of nerve cells, particularly dopamine-producing neurons, was evident in brains of the two Parkinson’s model rats relative to controls. These dopaminergic neurons were identified by the presence of a protein called tyrosine hydroxylase, or TH.

But between animals in the disease model groups, rats treated with lacosamide had a substantially better total nerve cell and dopamine-producing neuron count, the latter measured by TH presence, than those left untreated.

These findings suggest that lacosamide “may be effective in halting Parkinson’s disease-related neuronal death,” the researchers wrote.

Parkinson’s rats also showed significantly higher brain levels of malondialdehyde (MDA), a marker of oxidative stress, than did healthy controls.

Oxidative stress is a type cellular damage that arises by an imbalance between the body’s production of potentially harmful reactive oxygen species and its ability to neutralize them. This process has been implicated in Parkinson’s-associated neurodegeneration.

Likewise, significantly higher levels of TNF-alpha, a marker of inflammation, and lower levels of homovanillic acid (HVA), one of the main metabolites of dopamine that indicates dopaminergic neuron loss, were evident in the disease model compared with control rats.

Lacosamide treatment considerably reduced MDA and of TNF-alpha levels, and boosted the levels of HVA in the animals’ brains.

“According to our results, lacosamide has a beneficial impact on HVA levels as well as neuron counts, indicating that it could be a good alternative for treating Parkinson’s disease (PD) by reducing the death of dopaminergic neurons,” the researchers wrote.

“Even though our findings are promising, we recognise that more preclinical and clinical research is necessary to completely assess lacosamide’s effectiveness” as a Parkinson’s treatment, they added.