Commonly prescribed drugs
Alistair Burns, Michael A Horan, John E Clague, Gillian McLean in Geriatric Medicine for Old-Age Psychiatrists, 2005
L-dopa is the amino acid precursor of dopamine, and boosts the level of the neurotransmitter in the striatum. It is given with an extracerebral dopa- decarboxylase inhibitor to reduce peripheral conversi�n of L-dopa to dopamine, and therefore limits the peripheral side-effects such as nausea and vomiting. Benserazide is the inhibitor in co-beneldopa (dose expressed in terms of L-dopa dose: initiate 50 mg once or twice a day, increasing by 50 mg every 3-4 days according to response; for example, Madopar� con- tains 50 mg of L-dopa, 12.5 mg of benserazide, and is also available in 125- and 250-mg formulations and may be dispersed in water or orange squash - not orange juice - or swallowed whole; modified-release versi�n is available), and carbidopa in co-careldopa. The equivalent of co-careldopa is Sinemet�, which should be given in a similar regime and is available as 62.5, 110, 125 and 275 mg). A modified-release versi�n is available. These preparations are useful in people who are elderly and frail with co-morbid illness and severe symptoms. Therapy should be initiated at a low dose and increased in small steps, and the final dose should be the minimum needed, and intervals between doses should be bespoke. Entacapone preven�s the peripheral breakdown of L-dopa and may be helpful with co-careldopa and co-beneldopa, and there is end-of-dose deterioration.
Clinical specialties
Andrew Schofield, Paul Schofield in The Complete SAQ Study Guide, 2019
An 81-year-old man is referred to the neurology department by his GP. He has developed a tremor, and his GP is concerned he may have developed Parkinson’s disease. The neurologist agrees and starts levodopa, in combination with benserazide (co-beneldopa/Madopar). What is Parkinson’s disease? (1)Give the other two key features of Parkinson’s disease. (2)Name two other features of Parkinsonism. (2)Name two other causes of Parkinsonism. (2)Why is levodopa often used in combination with another drug, such as benserazide or carbidopa? (1)Why is levodopa commonly not used in younger patients with Parkinson’s disease? (1)The next patient in the clinic is an 80-year-old man who also has a tremor. The tremor is worse when he is anxious, and affects his arms more than his legs. He has found that a small glass of whisky settles the tremor almost completely.What is your diagnosis? (1)
A history of Parkinson’s disease
Jeremy Playfer, John Hindle, Andrew Lees in Parkinson's Disease in the Older Patient, 2018
Following publication of the efficacy of levodopa, Dr Oliver Sacks, who was a staff physician at Mount Carmel Hospital in New York, utilised this drug in the treatment of patients with encephalitis lethargica, and in his book Awakenings, he tells the moving story of the results of treatment.13 With increasing use of levodopa it soon became clear that the effects of treatment were not long-lasting, and problems of abnormal involuntary movements developed. Strategies to combat these difficulties included development of drugs to block the breakdown of levodopa in the blood and the use of Benserazide and Carbidopa combined with levodopa. Subsequent developments have tried to improve on the ‘gold-standard’ effect of levodopa and to minimise the consequence of long-term levodopa treatment.
Targeting glucose metabolism to develop anticancer treatments and therapeutic patents
Published in Expert Opinion on Therapeutic Patents, 2022
Yan Zhou, Yizhen Guo, Kin Yip Tam
Benserazide [15,41] (1–8) is an approved drug in the UK for the treatment of Parkinson’s disease. It is a peripheral aromatic L-amino acid decarboxylase inhibitor and is often combined with levodopa in clinical practice. Li et al. used a structure-based virtual ligand screening method to screen the FDA-approved drug database and found that 1–8 was a selective HK2 inhibitor [42] (Enzyme inhibition IC50: 5.52 ± 0.17 μM). As a clinically used drug, 1–8 has clear pharmacokinetics, pharmacodynamics, and low toxicity, which greatly facilitates the development of 1–8 and its derivatives as anti-tumor drugs. Moreover, 1–8 was found to reduce the glucose uptake rate, lactate production, and intracellular ATP levels of cancer cells, as well as depolarize the cancer cell mitochondrial membrane potential leading to apoptosis. These results suggested 1–8 might be a very promising anticancer drug candidate.
Nanocarrier for levodopa Parkinson therapeutic drug; comprehensive benserazide analysis
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Mehdi Yoosefian, Elham Rahmanifar, Nazanin Etminan
Parkinson’s disease is thought to be caused by too little of dopamine in the brain [2]. To help controlling movement, levodopa, precursor to the neurotransmitter dopamine, changes into dopamine in the brain. The compound benserazide (BZ) (DL-serine-2-[(2,3,4-trihydroxyphenyl)methyl] hydrazide) (C10H15N3O5) an irreversible inhibitor of peripheral aromatic L-amino acid decarboxylase (AADC), with L-Dopa (LD) is a combined therapy for age-related neurodegenerative disorder, Parkinson disease. Most LD is decarboxylated to dopamine (D) before it reaches the brain since that is unable to cross the brain–blood barrier. Drug inhibited dopamine decarboxylate allows dopamine to build up solely in brain instead. BZ at the recommended therapeutic dose not crossing the blood–brain barrier to any significant degree and combined therapy with levodopa reduces the amount of LD required for optimal therapeutic benefit and permits an earlier response to therapy and it is rapidly absorbed after oral administration. Benserazide prevents the breakdown of levodopa in the bloodstream and inhibits the aforementioned decarboxylation, so more levodopa can enter the brain and also reduce some of levodopa’s side effects [3,4].
Practical pearls to improve the efficacy and tolerability of levodopa in Parkinson’s disease
Published in Expert Review of Neurotherapeutics, 2022
Abhishek Lenka, Gianluca Di Maria, Guillaume Lamotte, Laxman Bahroo, Joseph Jankovic
While the risk of nausea and vomiting is minimized with the coadministration of carbidopa or benserazide with levodopa, some patients may still experience these symptoms during the initial few days or weeks of the levodopa therapy. In addition to carbidopa, antiemetics that do not block central dopamine receptors, such as trimethobenzamide, domperidone, and ondansetron, may be considered for symptomatic treatment of nausea/vomiting. Unfortunately, trimethobenzamide (Tigan) was recently discontinued by the manufacturer and as noted above, domperidone is not available in the US. There are no trials of ondansetron for the treatment of nausea/vomiting in PD; however, it may be considered as a treatment of levodopa-related nausea as it is a non-dopamine blocking agent and has good adverse effect profile [72]. The adverse effects of ondansetron (headache, stomach cramps, diarrhea, mild transaminitis) are mild, reversible, and usually are not dose-dependent [73].
Related Knowledge Centers
- Peripheral Nervous System
- Aromatic L-Amino Acid Decarboxylase
- Aromatic L-Amino Acid Decarboxylase Inhibitor
- Blood–Brain Barrier
- Parkinson's Disease
- L-Dopa
- British Approved Name
- Carbidopa
- Restless Legs Syndrome
- Precursor