Levodopa

Levodopa produces at 25-200 μM concentrations a dose-dependent reduction of 3H-DA uptake in foetal rat midbrain cultures. Levodopa results in a decrease in the number of viable cells and tyrosine hydroxylase (TH) positive neurones, plus disruption of the overall neuritic network. ^[1] Levodopa induces dyskinesia in the absence of dopamine by excessive inhibition of neurons of the putamen-globus pallidus (GPe) projection and subsequent disinhibition of the globus pallidus (GPe). Levodopa results in a decrease in cytochrome oxidase messenger RNA expression in the globus pallidus (GPi). ^[2]

Levodopa elicits the development of a variety of abnormal movements in monkeys with parkinsonism induced by the neurotoxin MPTP. Levodopa administrations result in an ectopic induction of the dopamine D3receptor expression in the CdPu in 6-OHDA-lesioned rats. ^[3] Levodopa (50 mg/kg) increases anandamide concentrations throughout thebasal ganglia via activation of dopamine D1/D2 receptors in intact rats. Levodopa produces increasingly severe oro-lingual involuntary movements which are attenuated by the cannabinoid agonist R(+)-WIN55,212-2 (1 mg/kg) in lesioned rats. ^[4] Levodopa administration reverses the up-regulation of D2 dopamine receptors seen in severely lesioned rats provided evidence that Levodopa reaches a biologically active concentration at the basal ganglia. ^[5]