Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용
Levodopa
레보도파 · L-DOPA · 3,4-DIHYDROXY-L-PHENYLALANINE · L-3,4-DIHYDROXYPHENYLALANINE · DIHYDROXYPHENYLALANINE · 3-(3,4-DIHYDROXYPHENYL)-L-ALANINE · L-Dihydroxyphenylalanine · Levedopa
식별자 및 물리적 특성
| CAS No. | 59-92-7 |
|---|---|
| 분자식 | C9H11NO4 |
| 평균 분자량 | 197.19 g/mol |
| 단동위원소 질량 | 197.06880783 g/mol |
| SMILES | N[C@@H](Cc1ccc(O)c(O)c1)C(=O)O |
| InChIKey | WTDRDQBEARUVNC-LURJTMIESA-N |
| PubChem CID | 6047 |
| ChEMBL | CHEMBL1009 |
| ChEBI | CHEBI:15765 |
| EC No. | 200-445-2 |
| DTXSID | DTXSID9023209 |
화학 및 물리적 성질
| XLogP | -2.7 |
|---|---|
| 극성 표면적 | 104 |
| 수소 결합 공여자 수 | 4 |
| 수소 결합 수용자 수 | 5 |
| 회전 가능 결합 수 | 3 |
| 무거운 원자 수 | 14 |
| 형식 전하 | 0 |
| 복잡도 | 209 |
| 물질 분류 | Biological Agents -> Amino Acids and Derivatives |
| 의약품 | Pharmaceuticals -> Listed in ZINC15 |
| LogP(분배 계수) | log Kow = -2.39 |
| 냄새 | Odorless100.00%에서. 냄새 없는 |
| 맛 | Tasteless |
| Color/Form | Colorless to white crystals or crystalline powderneedles from water |
| 용해도 | 5mMReadily sol in dil hydrochloric and formic acidspractically insol in ethanol, benzene, chloroform, ethyl acetateIn water, 5,000 mg/l @ 20 °C5.0 mg/mL물에는 약간 용해되고 에탄올에는 거의 용해되지 않습니다(96%). 1M 염산에는 잘 녹고 0.1M 염산에는 거의 녹지 않습니다. |
| Human Drugs | Breast FeedingLactationMilk, HumanAntiparkinson AgentsDopamine AgentsFDA approved drugs -> Active ingredientEMA approved medicines: Human medicinePharmaceuticals |
| Decomposition | When heated to decomposition it emits toxic fumes of /nitrogen oxides/. |
| 녹는점 | 284-286 °C285 °C276-278 °C (lit.) |
| Optical Rotation | Specific optical rotation: -13.1 deg @ 13 °C/D (c= 5.12 in 1 N HCl)max absorption (0.001 N HCl): 220.5 nm (log e= 3.79)280 nm (log e= 3.42) |
| Physical Description | Colorless to white odorless solid[Merck Index] White crystalline solid[Sigma-Aldrich MSDS] |
| 끓는 점 | 334.28°C (rough estimate) |
| 밀도 | 1.3075 (rough estimate) |
| 굴절률 | -12 ° (C=5, 1mol/L HCl) |
| 저장 조건 | 2-8°C |
| 물리적 상태 | 결정성 분말 |
| pKa(산도 계수) | 2.32(at 25℃) |
| 색상 | 흰색에서 크림색 |
| 향취 유형 | 냄새 없는 |
| 용해도 | 물에 약간 용해되고 묽은 염산과 포름산. 에탄올에 불용성. |
| Merck | 14,5464 |
| BRN | 2215169 |
| 안정성 | 안정적인. 강한 산화제와 호환되지 않습니다. 빛과 공기에 민감합니다. |
| 주요 응용 | 펩타이드 합성 |
| InChI | 1S/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1 |
| InChIKey | WTDRDQBEARUVNC-LURJTMIESA-N |
| SMILES | N[C@@H](Cc1ccc(O)c(O)c1)C(O)=O |
| LogP(분배 계수) | -1.154 (est) |
| NIST | Levodopa(59-92-7) |
| EPA | Levodopa (59-92-7) |
화학적 성질
L-Dopa [59-92-7], levodopa, crystallizes as colorless, odorless, and tasteless needles from water, mp 276-278℃(decomp.). It is freely soluble in dilute hydrochloric and formic acids but practically insoluble in ethanol, benzene, chloroform, and ethyl acetate. Solubility in water is 66 mg/40 mL. In the presence of moisture, l-dopa is rapidly oxidized by atmospheric oxygen, with darkening.
안전 및 규제
| GHS 분류 | DangerH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 208 reports by companies from 24 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 규제 정보 | Hazard Traits - Developmental ToxicityStatus: Active Update: 16-03-2020 https://echa.europa.eu/registration-dossier/-/registered-dossier/282793,4-Dihydroxy-L-phenylalanine: Does not have an individual approval but may be used under an appropriate group standard |
| 기타 안전 정보 | IMAP assessments - L-Tyrosine, 3-hydroxy-: Environment tier I assessment |
| 유해성 요약 | Teratogenic effects, early post-natal loss, and significantly delayed parturition observed in experimental animals at high dosesNo evidence of adverse effects to pregnancy outcome in humans[REPROTOX] The primary target of toxicity is the cardiovascular system, with additional effects associated with the gastrointestinal tract and nervous system[INCHEM PIMs] A skin and strong eye irritantHarmful by ingestionTargets the heart[Sigma-Aldrich MSDS] See DL-Dihydroxyphenylalanine. |
| FDA 요건 | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl levodopa, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Special Reports | REVIEW WITH 65 REF ON ROLE OF ENDOGENOUS AMINES IN TREATMENT OF PARKINSON'S WITH L-DOPA. |
| Hazard Classes and Categories | Acute Tox. 4 (100%) |
| 처리 방법 | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| 체내 부담 | ... Mean plasma levodopa concn ranged between 0.45-7.07 ug/ml & peak concns between 0.95-13.75 ug/ml. In 44 of 58 dosing events, an oral dose of levodopa was related to a peak in plasma concn. ... |
| Treatment | Hospitalization is advised, and general supportive measures should be employed, along with immediate gastric lavage and repeated doses of charcoal over time. This may hasten the elimination of entacapone in particular, by decreasing its absorption/reabsorption from the GI tract. Intravenous fluids should be administered judiciously and an adequate airway maintained. The adequacy of the respiratory, circulatory and renal systems should be carefully monitored and appropriate supportive measures employed. Electrocardiographic monitoring should be instituted and the patient carefully observed for the development of arrhythmiasif required, appropriate antiarrhythmic therapy should be given. The possibility that the patient may have taken other drugs, increasing the risk of drug interactions (especially catechol-structured drugs) should be taken into consideration. Hemodialysis or hemoperfusion is unlikely to reduce entacapone levels due to its high binding to plasma proteins. (L1712) |
| 상호 작용 | The pharmacokinetics of levodopa (LD) with & without pramipexole in men & postmenopausal women with Parkinson's disease /were studied/. Patients on stable dose of carbidopa/LD were randomized to receive escalating doses of placebo or pramipexole over 7 wks. LD & pramipexole pharmacokinetics were performed after a single test dose 25/100 of carbidopa/LD, before initiation of pramipexole or placebo, at 1.5 mg/d & 4.5 mg/d of pramipexole or placebo. Compared to men, women had greater LD bioavailability. Pramipexole did not alter LD bioavailability, & pramipexole pharmacokinetics were equivalent in men & women.Admin of levodopa with nonspecific inhibitors of MAO, such as phenelzine & tranylcypromine, markedly accentuates the actions of levodopa & may precipitate life-threatening hypertensive crisis & hyperpyrexianonspecific MAO inhibitors always should be discontinued at least 14 days before levodopa is admin (note that this prohibition does not include the MAO-B subtype-specific inhibitor selegiline, which, as discussed below, often is admin safely in combination with levodopa). Abrupt withdrawal of levodopa or other dopaminergic medications may precipitate the neuroleptic malignant syndrome more commonly observed after treatment with dopamine antagonists.Conventional antipsychotic agents, such as the phenothiazines, ... may cause marked worsening of parkinsonism, probably through actions at the D2 dopamine receptor.TRICYCLIC ANTIDEPRESSANTS...GIVEN CONCOMITANTLY WITH LEVODOPA EVOKE HYPERTENSIVE CRISES.For more Interactions (Complete) data for LEVODOPA (33 total), please visit the HSDB record page. |
| 유해 작용 | The common adverse effects of Levodopa treatment are nausea, dizziness, headache, and somnolence. Increasing carbidopa is recommended to relieve nausea, and domperidone can be helpful if additional carbidopa is ineffective. Special precautions are necessary for elderly patients because they may be more sensitive to the central nervous system (CNS) effects. The most common side effects in older patients taking levodopa can be confusion, hallucinations, delusions, psychosis, and agitation. There may be a greater risk of hip fractures in older adults due to levodopa mildly increasing homocysteine levels as an adverse effect. Patients presenting with an idiopathic parkinsonian disorder and who are on levodopa can also develop low serum vitamin B12, elevated methylmalonic acid levels, and a greater chance of sensorimotor peripheral neuropathy. |
| 노출 경로 | Levodopa is rapidly absorbed from the proximal small intestine by the large neutral amino acid (LNAA) transport carrier system. |
| Milk Concentrations | ...DRUG...MAY APPEAR IN MILK. |
| 독성 요약 | IDENTIFICATION: Levodopa is used as a drug for treating Parkinsons disease. Levodopa is white or almost white crystalline powder, which darkens on exposure to air and light. Levodopa is odourless and almost tasteless. It is slightly soluble in water. Soluble in aqueous solutions of mineral acids and alkali carbonatespractically insoluble in alcohol, chloroform, and ether. HUMAN EXPOSURE: Main risks and target organs: The principal target organ is Central Nervous System. The main risks are cardiovascular. Additional risks are associated with the gastrointestinal tract, and the peripheral as well as the central nervous system. Summary of clinical effects: Nausea and anorexia commonly occur and may be accompanied by vomiting. Another effect includes abdominal pain, constipation, diarrhea and dysphagiadyspepsia and gastrointestinal bleeding. The commonest cardiovascular effect is postural hypotension, with faintness and dizziness. There may be palpitations often accompanied by excess sweating. Cardiac arrhythmias, particularly atrial and ventricular ectopic beats, have been reported and hypertension has occasionally occurred. Psychiatric symptoms include agitation, anxiety, elation and insomnia or some times drowsiness and depression. More severe effects include aggression, paranoid delusions, hallucinations, suicidal behaviour and unmasking of dementia. Involuntary movements are very common and usually start in the mouth, jaws or tongue. Abnormal limb movements often develop after several months and severe choreoathetoid movements may also occur after prolonged high doses. Oculogyric movements may rarely be exacerbated and muscle twitching and blepharospasm occur occasionally. Headache, weakness, ataxia, and rarely paraesthesia and convulsions have occurred. Polyuria, incontinence, and difficulty in micturition may occur. Blurred vision, mydriasis, diplopia and glaucoma are rare. Uncommon effects include transient rises in tests for liver function and blood urea nitrogen, abnormal respiratory movements, loss of hair, skin rashes, activation of Horner's syndrome, weight changes, and rarely agranulocytosis or hemolytic anemia. Administration without benserazide: The dose producing maximal improvement with tolerated side effect must be determined and carefully titrated for each individual patient. Contraindications: Levodopa is contraindicated for melanoma and glaucoma in patients with known hypersensitivity to the drug. Levodopa should be administered cautiously to patients with severe cardiovascular or pulmonary disease, asthma, renal, hepatic or endocrine disease. Care should be exercised in administering levodopa to patients with history of myocardial infarction who have residual atrial nodal or ventricular arrhythmias. If levodopa is necessary in this type of patient, it should be used in a facility with a coronary care unit or an intensive care unit. One must be on the alert for the possibility of upper gastrointestinal hemorrhage in those patients with a past history of peptic ulcer disease. Levodopa is contraindicated in patients with severe psychotic disorders, it should be used with caution in patients with psychiatric disturbance. This drug should not be used in pregnancy and should not be used in nursing mothers. The safety under the age of 12 has not been established. Routes of entry: Oral: The route of entry of levodopa is oral. Absorption by route of exposure: Levodopa is rapidly absorbed from the small intestine by an active transport system for aromatic amino acids. Concentrations of drug in plasma usually peak between 0.5 and 2 hours after an oral dose. The rate of absorption of levodopa is greatly dependent upon the rate of gastric emptying, the pH of gastric juice and the length of time the drug is exposed to the degradative enzymes of the gastric mucosa and intestinal flora. Hyperacidity of gastric juice, and competition for absorption sites in the small intestine by amino acids each may interfere with the bioavailability of vodopa. Distribution by route of exposure: It is widely distributed to most body tissues, but less to the central nervous system (CNS). Little unchanged drug reaches the cerebral circulation and probably less than 1% penetrates into the CNS. Biological half-life by route of exposure: Levodopa has relatively short plasma half-life of 1 to 3 hours. Metabolism: More than 95% of levodopa is decarboxylated by the widely distributed extracerebral aromatic l-amino acid decarboxylase. The drug is extensively decarboxylated in its first passage through the liver, which is rich in decarboxylase. A small amount is methylated to 3-0-methyldopa, which accumulates in the CNS due to its long half-life. Most is converted to dopamine, small amounts of which in turn are metabolized to norepinephrine and epinephrine (adrenaline). Biotransformation of dopamine proceeds rapidly to yield the principal excretion products, 3-4-dihydroxy-phenylacetic acid (DOPAC) and 3-methoxy-4-hydroxy-phenylacetic acid (homovanillic acid, HVA). At least 30 metabolites of levodopa have been identified. The evidence indicates that the metabolism of levodopa may be accelerated during prolonged therapy possibly due to enzyme induction. Elimination by route of exposure: Oral: Excretion: Metabolites of dopamine are rapidly excreted in the urine80% of a radioactively labelled dose is recovered within 24 hours. The principal metabolites DOPAC and HVA account for up to 50% of the administered dose. Negligible amounts are found in the feces. Mode of action: Toxicodynamics: Peripheral decarboxylation of levodopa markedly increases the concentration of dopamine in blood. Dopamine is a pharmacologically active catecholamine with prominent effects of alpha and beta adrenergic receptors, and this point give the potentially toxic effects. Pharmacodynamics: Levodopa is the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the basal ganglia. This is thought to be the mechanism whereby levodopa relieves symptoms of Parkinson's disease, because it replaces depleted brain dopamine in these patients. Interactions: Doses of pyridoxine that are only modestly in excess of the recommended dietary allowance enhance the extracerebral metabolism of levodopa at this step. Antipsychotic drugs, such as phenothiazines, butyrophenones and reserpine can produce a parkinsonism-like syndrome, and since these drugs interfere with the therapeutic effects of levodopa, they are contraindicated. Therefore the phenothiazines should not be used to combat the emetic effect of levodopa. Nonspecific monoamine oxidase inhibitors interfere with inactivation of dopamine, norepinephrine and other catecholamines. Hence, they unpredictably exaggerate the central effects of levodopa and its catecholamine metabolites. Hypertensive crisis and hyperpyrexia are very real and dangerous sequelae of concurrent administration of two such drugs. Anticholinergic drugs such as phenidyl, benztropine, procyclidine and others act synergistically with levodopa to improve certain symptoms of parkinsonism, especially tremor. However, large doses of anticholinergic drugs can slow gastric emptying sufficiently to cause a delay in reabsorption of levodopa by the small intestine. The effect of levodopa is enhanced by amantadine, benserazide, carbidopa, atropine and amphetamine. Concurrent administration of levodopa with guanethidine, methyldopa and other antihypertensive agents may cause increased hypotension. Cardiac arrhythmias due to levodopa may be augmented by anaesthetic agents, such as cyclopropane or halothane. Sympathomimetic agents such as epinephrine (adrenaline) or isoprenaline may also enhance the cardiac side effects of levodopa. Beta-adrenergic blocking agents such as propranolol may enhance the action of levodopa on tremor and diminish the cardiac side effects. In some patient the administration of antacids with levodopa may enhance the gastrointestinal absorption of levodopa. Main adverse effects: Rarely, oculogyric crises, sense of stimulation, hiccups, edema, loss of hair hoarseness, priapism and activation of latent Horner's syndrome have been observed. Elevation of blood urea nitrogen, SGOT, SGPT, LDH, bilirubin, alkaline phosphatase or protein-bound iodine have been reported, occasional reduction in WBC, hemoglobin and haematocrit have been noted. Leucopenia has occurred and requires cessation at least temporarily, of levodopa administration. Acute poisoning: Ingestion: Spasm or closing of eyelids are possible early sign of overdose. Nausea, vomiting, cardiac arrhythmias, involuntary movements of the body, including the face, tongue, arms, hand, head, and upper bodychoreiform and other involuntary movements occur in 50% to 80% of patients. This effect is dose related. Psychiatric disturbances are usually present. Hypotension, hemolytic anemia, urinary retention, duodenal ulcer, sialorrhea, ataxia, abdominal pain, dry mouth, nightmares, tachypnea, bruxism, confusion, insomnia also occur. Special risks: Pregnancy, breast-feeding: Levodopa represent a risk for pregnancy and the nursing mother. Use of medication should be carefully considered in conjunction with bronchial asthma, emphysema and other severe pulmonary cardiovascular diseasehistory of convulsive disorders, diabetes, endocrine diseases, glaucoma, hepatic function impairment, history of suspected melanoma, history of myocardial infarction with residual history of peptic ulcer, psychotic states, renal function impairment, urinary retention. ANIMAL/PLANT STUDIES: Teratogenicity: Studies in rabbits have shown that levodopa causes visceral and skeletal malformations in offspring.Studies have shown that levodopa toxicity can damage neuronal cells. The formation of free radicals once the body oxidizes levodopa can induce apoptosis. Also, dopamine, norepinephrine, and epinephrine levels can rise in the blood when levodopa undergoes decarboxylation in the periphery. The rise in catecholamines activates alpha- and beta-adrenergic receptors, resulting in toxic effects. In pregnant women, levodopa crosses the placenta and can be metabolized by the fetus. Unfortunately, there is insufficient information to make an appropriate decision regarding the use of levodopa in pregnant women. The drug is excreted in breast milk, and thus, caution is advised when administering the medication to nursing women. Supportive measures are necessary to treat toxicity, such as gastric lavage, airway maintenance, and intravenous fluid administration.Striatal dopamine levels in symptomatic Parkinson's disease are decreased by 60 to 80%, striatal dopaminergic neurotransmission may be enhanced by exogenous supplementation of dopamine through administration of dopamine's precursor, levodopa. A small percentage of each levodopa dose crosses the blood-brain barrier and is decarboxylated to dopamine. This newly formed dopamine then is available to stimulate dopaminergic receptors, thus compensating for the depleted supply of endogenous dopamine. |
| Natural Pollution Sources | /L-DOPA/ IS NATURALLY OCCURRING FORM OF DOPA...THE BIOLOGICAL PRECURSOR OF CATECHOLAMINES. |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ Application of levodopa to the eyes of normal people has shown that it can induce mydriasis at sufficiently high concentrations./CASE REPORTS/ The case of a 70-yr-old woman with a long history of Parkinson's disease taking Sinemet-275 (25 mg carbidopa, combination, 250 mg levodopa), at a maximum dose of 8 tablets/day for 13 yr, who was noted to have intense black pigmentation confined to the costal cartilages at necropsy, is reported. It was suggested that failure to metabolize high plasma levels of levodopa in the presence of a dopa-decarboxylase inhibitor had resulted in the deposition of dihydroxyphenylalanine in the costal cartilage of the patient./CASE REPORTS/ Acute overdose was reported in a 61-yr old man following ingestion of 100 g of levodopa. He experienced hypertension initially, followed by hypotension for a few hrs, mild nausea, & severe anorexia that gradually resolved over 1 wk. He had insomnia for about 1 wk, confusion for 2 days, & agitation for 3-4 days. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)LevodopaDILI NegativeOralDOI:10.1016/j.drudis.2019.09.022 |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Acute Exposure/ STUDIES ON RETINAL ACTIVITY IN CATS HAVE SHOWN DECR IN AMPLITUDE OF ELECTRICAL POTENTIAL IN OPTIC TRACT EVOKED BY EXPOSURE OF EYE TO LIGHT FLASHES, AFTER IV ADMIN OF L-DOPA.../LABORATORY ANIMALS: Acute Exposure/ AFTER ORAL ADMIN OF L-DOPA TO CALVES, PLASMA CONCN OF L-DOPA, DOPAMINE, NOREPINEPHRINE & PARATHYROID HORMONE INCREASED./LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ This study assessed whether or not levodopa induces dyskinesias in normal (ie, unlesioned) squirrel monkeys. All six animals treated twice daily with levodopa (15 mg/kg with carbidopa by oral gavage) for two weeks developed choreoathetoid dyskinesias, whereas none of the vehicle-treated animals displayed any abnormal movements. These dyskinesias did not merely reflect a generalized motor activation as locomotion was actually suppressed. The present data demonstrate that preexisting nigrostriatal damage is not necessary for the development of levodopa-induced dyskinesias. |
| 수질 위해 등급(WGK) | 3 |
| TSCA 등재 상태 | TSCA listed |
| RTECS 번호 | AY5600000 |
| 독성 | LD50 in mice (mg/kg): 3650 ±327 orally, 1140 ±66 i.p., 450 ±42 i.v., >400 s.c.in male, female rats (mg/kg): >3000, >3000 orally624, 663 i.p.>1500, >1500 s.c. (Clark) |
| 관세 코드 | 29225090 |
| 위험 문구(R) | 22-36/37/38-20/21/22 |
| 위험 표시 | Xn |
| 안전 문구(S) | 26-36-24/25 |
| 기존화학 물질 | KE-10853 |
| F 고인화성물질 | 10-23 |
| 위험 등급 | Acute Tox. 4 OralEye Irrit. 2Skin Irrit. 2STOT SE 3 |
| 저장 분류 | 11 - Combustible Solids |
| 유해 물질 데이터 | 59-92-7(Hazardous Substances Data) |
용도
개요
Levodopa is an amino acid precursor of dopamine with antiparkinsonian properties. Levodopa is a prodrug that is converted to dopamine by DOPA decarboxylase and can cross the blood-brain barrier. When in the brain, levodopa is decarboxylated to dopamine and stimulates the dopaminergic receptors, thereby compensating for the depleted supply of endogenous dopamine seen in Parkinson's disease. To assure that adequate concentrations of levodopa reach the central nervous system, it is administered with carbidopa, a decarboxylase inhibitor that does not cross the blood-brain barrier, thereby diminishing the decarboxylation and inactivation of levodopa in peripheral tissues and increasing the delivery of dopamine to the CNS.
용도
Levodopa is an immediate precursor of dopamine and product of tyrosine hydroxylase. It derived from vanillin is widely used for treatment of Parkinson’s disease, most often in combination with peripheral decarboxylase inhibitors such as benserazide and carbidopa.
일반 설명
Levodopa belongs to a group of the most effective drugs for treating the type of Parkinsonism not caused by medicinal agents. The first significant breakthrough in the treatment of PDcame about with the introduction of high-dose levodopa. Fahn referred to this as a revolutionary development intreating parkinsonian patients. The rationale for the use oflevodopa for the treatment of PD was established in theearly 1960s. Parkinsonian patients were shown to have decreasedstriatal levels of DA and reduced urinary excretionof DA. Since then, levodopa has shown to be remarkablyeffective for treating the symptoms of PD.