Sinemet is a drug approved by the U.S. Food and Drug Administration (FDA) for the treatment symptoms associated with Parkinson’s disease. The drug is a combination of two amino-acids: levodopa (a central nervous system agent) and carbidopa (an agent inhibiting an enzyme called decarboxylase). Together, these two components increase the level of dopamine in the brain, which normally is low in Parkinson’s disease patients, leading to the motor impairments associated with the disease.

Merck commercializes Sinemet as tablets in three strengths with different concentrations of levodopa and carbidopa. Sinemet 25-100 contains 25 mg of carbidopa and 100 mg of levodopa, Sinemet 10-100 contains 10 mg of carbidopa and 100 mg of levodopa, and Sinemet 25-250, contains 25 mg of carbidopa and 250 mg of levodopa.

A new formulation of Sinemet with a controlled-release (CR) was approved by the FDA in 2014. Sinemet CR tablets contain either 50 mg of carbidopa and 200 mg of levodopa, or 25 mg of carbidopa and 100 mg of levodopa.

How Sinemet works

The underlying cause for the tremors, stiffness, and slowness of movements associated with Parkinson’s disease is the reduced level of dopamine (a neurotransmitter molecule) in the brain. However, the direct administration of dopamine is ineffective in the treatment of Parkinson’s disease because it cannot cross the blood-brain barrier and reach the brain.

Levodopa is a metabolic precursor of dopamine or a compound that participates in the chemical reaction that produces dopamine, which is able to cross the blood-brain barrier and reach the brain, where it can be converted to dopamine.

Carbidopa works by preventing the breakdown of levodopa by decarboxylase enzymes. Because it cannot cross the blood-brain barrier, carbidopa ensures the safe delivery of levodopa to the brain, where it becomes exposed to the action of the decarboxylases that generate dopamine.

The combination of carbidopa and levodopa enhances levodopa’s potential of action because it enables the use of much lower doses of levodopa (80% less), which helps reduce the drug’s side effects, which include nausea and vomiting.

Studies with Sinemet

Bial designed two clinical trials from 2012 to 2015 to investigate the effect of a drug called Opicapone on the beneficial effects of levodopa in Parkinson’s disease patients undergoing treatment with Sinemet (NCT02169479), or Sinemet CR (NCT02169453). Results showed that 50 mg once-daily of Opicapone achieved significant reductions (two hours) in absolute “off-time” and enhanced the beneficial effects of levodopa in Parkinson’s disease patients with motor fluctuations.

Intec Pharma is recruiting participants to join a 27-week, Phase 3, multicenter, global study in adults with fluctuating Parkinson’s disease (NCT02605434). The aim of the trial is to determine whether a gastric retentive carbidopa-levodopa treatment (Accordion Pill) is more effective than an immediate release carbidopa-levodopa treatment (Sinemet) in reducing motor fluctuations such as “off-time” events.

One trial is recruiting Parkinson’s disease patients in Canada for a two-week, Phase 4 study (NCT03111485) to assess whether long-acting treatment with Sinemet CR, taken at night time, improves obstructive sleep apnea.

Patients also are being recruited to enter trials to assess the effect of the carbidopa-levodopa combination in the treatment of other conditions, such as age-related macular degeneration (NCT03023059NCT03022318) , retinitis pigmentosa (NCT02837640), stroke (NCT02386475), back pain (NCT01951105), albinism (NCT01663935), depression (NCT02513485) and substance abuse (NCT02080819 and  NCT00439049).
