Legendary drug - L-dopa past and present life
L-dopa is used to treat Parkinson's disease has been going through more than 50 years of ups and downs. It is still considered the most effective anti-Para drug. It is of milestone significance to the treatment of Parkinson's disease. Just imagine, if there is no levodopa, then we will be helpless in the face of the ancient ghost of Parkinson's disease!
Today I want to take you to know the past and present of this legendary drug - L-dopa.
Dating back to the discovery of levodopa, it requires the history to be turned back to 1957, 140 years after British scholar James Parkinson first reported the disease.
Introduction
levodopa— dopamine
1957 , Arvid Carlsson discovered that levodopa is a precursor substance that can be metabolized into dopamine in the body, and can reverse the impact of dopamine depletion in the brain caused by reserpine and improve the motor function of experimental animals. This is the first time that the scientific community has discovered the link between levodopa-dopamine. Arvid Carlsson also won the 2000 Nobel Prize in Physiological Medicine for this discovery.
Image source: Nobel Prize
Key
Dopamine-Parkinson's disease-levodopa
The connection between dopamine-levodopa-Parkinson's disease is another Austrian scientist Oleh Hornykiewicz.
Before this, Oleh Hornykiewicz had been studying the problem of dopamine and had a preliminary argument that "dopamine is a neurotransmitter with biological effects." Subsequently, the study found that reserpine depletes dopamine in the brain, and clinically found that reserpine causes Parkinson-like manifestations . Oleh Hornykiewicz has a bold guess Maybe the decrease in dopamine in the brain is the essence of Parkinson's disease! In order to verify his conjecture, he took the lead in proving that the caudate nucleus and putamen dopamine content in the basal ganglia of Parkinson's disease, through the study of brain specimens of 6 cases of Parkinson's disease, 2 cases of Huntington's disease, and 17 cases of normal people, the caudate nucleus and putamen do not have abnormal changes in the dopamine content in the brains of Parkinson's disease.
1961 , Oleh Hornykiewicz, together with Austrian geriatrician Walther Birkmayer, conducted the first clinical trial of levodopa in the treatment of Parkinson's disease. The study included 20 patients with Parkinson's disease, and the doses of levodopa were between 50 and 150 mg. The results showed a significant improvement in motor function in patients with bedriddenson's disease who were unable to move. They then tried to replicate the findings in a larger patient population, enrolling 200 patients receiving intravenous injection of levodopa. Unfortunately, only 20% of patients showed a slight improvement in symptoms, perhaps because of insufficient dose of levodopa.
Dawn
The era of levodopa
During this period, the scientific community has never stopped the research on levodopa in the treatment of Parkinson's disease, but without exception, no good progress has been made.
Until 1968, American pharmacologist George Cotzias et al., through continuous clinical trials, collected 28 patients with Parkinson's disease for levodopa treatment, with the initial dose of 100 mg/time, three times a day; according to the patient's tolerance, the increase was 200-300 mg every 2-4 days; until the efficacy was observed clinically, the dosage was stopped, and the maximum dose was not more than 8 g/day. The results of the study showed that there were very significant improvements in motor symptoms in 10 patients, and the average treatment dose in these 10 patients was 5.8 g/day. gives the appropriate dose, and the motor symptoms in patients with Parkinson's disease can be effectively relieved. These gratifying clinical research results officially announce the arrival of the levodopa era.
catalytic
New catalyst
New catalyst
In the 1960s, another great person appeared. His appearance made it possible for levodopa to achieve industrial production of , and he is the American chemist William Knowles.
William Knowles has produced A novel catalyst . Adding this catalyst can produce levodopa with a near-perfect purity in chemical reactions. This catalyst is widely used in the industrial synthesis of the pharmaceutical industry, including antibiotics, anti-infective drugs and heart disease drugs. Therefore, William Knowles won the Nobel Prize in Chemistry in 2001.
Image source from Nobel Prize
on the market
1970 In the past, Roche Group started the commercial production process of levodopa. The levodopa developed by its company was approved for listing in the United States, opening a new world for the treatment of Parkinson's disease.
pictures are from the Internet
However, the "symptom fluctuations" and "dyskinesia" caused by the short half-life of levodopa are relatively headaches.
So there is another second milestone on the anti-Pa Road - deep brain electrical stimulation (brain pacemaker surgery)
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