Synergistic actions of melatonin in combination with anti-parkinsonian drugs in experimental model of Parkinson’s disease

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive degeneration and loss of nigrostriatal dopaminergic neurons in the midbrain, A9 substantia nigra neurons leading to severe striatal dopamine (DA) depletion resulting in tremor, rigidity and hypokinesia (Carlsson, 2002). PD is named after James Parkinson who first described the disease as “Shaking Palsy” (Paralysis Agitans) in his classic monograph “An essay on the Shaking Palsy” (Parkinson, 1817). This debilitating disorder has no cure existing, and recent epidemiological studies suggest an increasing trend in its incidents; predicting an alarming 2-fold increase in affected population by 2030 in several countries (Dorsey et al., 2007). Currently used drugs for PD provides symptomatic relief, and are based on increasing the striatal levels of DA, or controlling the DA transmission. However, these drugs are generally short acting, and with time develop serious side effects. There are cases when the drugs need to be discontinued due to exacerbation of DA-mediated effects. At this juncture, there is a great need of alternative therapies, or designs that would effectively reduce the dose of drugs that causes ‘on-off’ effects, dyskinesias, other undesirable motor effects, non-motor complications, and slower the progression of the disease. One of such effective therapy is using a peripheral aromatic amino acid decarboxylase inhibitor, carbidopa along with L-3,4-dihydroxyphenylalanine (L-DOPA). The present study mainly addressed such alternative approaches so as to find better therapeutic agents that may synergize with the existing PD drugs.