The history of dopamine and levodopa in the treatment of Parkinson's disease

Abstract

The discoveries of dopamine as a neurotransmitter in the brain, its depletion in patients with Parkinson disease, and its replacement with levodopa therapy were major revolutionary events in the rise to effective therapy for patients with this disorder. This review describes these events and the persons who carried out these accomplishments. Their impact went beyond a single clinical entity of parkinsonism, for it opened up the beginning of a much better understanding of the role of dopamine in other neurologic movement disorders and also in many psychiatric diseases.

Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities

“…A significant finding from our work is that the reduction in the expression levels of Th and Tph2 and their corresponding neurotransmitter levels in the respective aminergic MeCP2-CKO animals are comparable to those observed in Mecp2 null/y animals, fully recapitulating the neurochemical and molecular defects. In addition, the unique behavioral phenotypes that we observed in the TH-and PET1-CKO mice are due to the absence of MeCP2 function in either dopaminergic and noradrenergic or serotonergic neurons, respectively, and these phenotypes have been linked to defects in the respective neurotransmitter systems in both humans and mice (4)(5)(6)(7)(8)(9)27). To explore the mechanism underlying the decrease in expression of the synthetic enzymes, we tested whether MeCP2 occupied the Th and Tph2 promoter regions and found that the promoter regions of both neurotransmitter synthesis genes are occupied by MeCP2.…”

“…For example, it is well established that decreased dopamine levels are linked to motor abnormalities in humans and in mice (9,41). Motor deficits are also prominent in girls and women with RTT (8,42).…”

“…It has been suspected that aminergic neurons malfunction in RTT, because the heightened anxiety, aggression, and mood alterations seen in RTT and MECP2 disorders are associated with abnormalities of the serotonergic system in other human disorders (4)(5)(6). Rigidity and movement abnormalities are associated with dysfunction of dopaminergic system (7)(8)(9). Autonomic dysfunction underlying breathing irregularities could be attributable to decreased norepinephrine (7,10).…”

Gut-Microbiota Link in Parkinson’s Disease: Current Perspectives

“…In 1912 Frederic Lewy described microscopic particles in affected brains, later named :Lewy bodies" [15].In 19919 Konstantin Tretiakoff reported that substantianigra was the main cerebral structure affected, but his findings was not widely accepted until it was confirmed by further studies published by Rolf Hassler in 1938 [15].In 1997,alpha-synucleain was found to be the main component of Lewy bodies by Spillantii,et al [17].Levodopa was first synthesized in 1911 by Casimir Funk.It entered the clinical practice in 1967 and brought about a revolution in the management of PD [18].By the late 1980s deep brain stimulation introduced by Alim Louis Benabid and colleagues at Grenoble, France, emerged as a possible treatment [19].…”

Electroanalytical Characterisation of Dopa Decarboxylase Inhibitors Carbidopa and Benserazide on Multiwalled Carbon Nanotube and Poly(Nile blue A) Modified Glassy Carbon Electrodes

“…However, medications are used to increase levels of dopamine in the brain of patients with PD and in this way slow down the progression of the disease, since motor symptoms are produced by a lack of dopamine. The main drugs used for Parkinson's disease are levodopa, dopamine agonists, and MAO-B inhibitors [3].…”