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Movement disorders
Published in Henry J. Woodford, Essential Geriatrics, 2022
The rationale for the use of levodopa is that it is converted to dopamine within the surviving neurons of the basal ganglia to help compensate for the loss of dopaminergic cells (giving dopamine would be ineffective because it cannot cross the blood-brain barrier). It is always given with a decarboxylase inhibitor (carbidopa or benserazide) to prevent excessive peripheral conversion of levodopa to dopamine, which would reduce cerebral availability and produce excessive adverse effects (mainly nausea, vomiting and orthostatic hypotension) (seeFigure 9.8).
Clinical specialties
Published in Andrew Schofield, Paul Schofield, The Complete SAQ Study Guide, 2019
Andrew Schofield, Paul Schofield
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)
Sleep dysfunction in Parkinson’s disease
Published in Jeremy Playfer, John Hindle, Andrew Lees, Parkinson's Disease in the Older Patient, 2018
Nocturnal akinesia is usually caused by night-time wearing off and strategies promoting overnight dopaminergic stimulation may be helpful. Sustained-release levodopa/benserazide significantly improved night-time akinesia (ability to turn in bed) and reduced total time awake in a 12-month open-label, non-comparative trial including 15 patients with PD and distressing nocturnal symptoms.84 Open-label comparative observational reports in PD patients with severe sleep disruption due to nocturnal motor symptoms suggest that cabergoline, the long-acting once-a-day dopamine agonist may be superior to levodopa or pergolide.85,86 Overnight apomorphine infusion also has been reported to be beneficial for nocturnal motor and non-motor symptoms of PD.87 These studies were performed prior to the availability of the PDSS and currently studies investigating the efficacy of controlled-release formulations of agents (such as ropinirole and rotigotine transdermal patch) on nocturnal akinesia are under way.
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].
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.
Comparative examination of levodopa pharmacokinetics during simultaneous administration with lactoferrin in healthy subjects and the relationship between lipids and COMT inhibitory activity in vitro
Published in Nutritional Neuroscience, 2022
Masahiro Nagai, Madoka Kubo, Rina Ando, Masayuki Ikeda, Hiroshi Iwamoto, Yasuhiro Takeda, Masahiro Nomoto
No significant changes were observed in the pharmacokinetics (AUC(0–240 min), Cmax, Tmax, and t1/2) of levodopa regardless of the concomitant administration of bLF. In addition, no significant changes were observed in the metabolites 3-OMD, DOPAC, and HVA. In mice, the administration of levodopa (approximately 58 mg/kg), carbidopa (approximately 14 mg/kg), and bLF (580 mg/kg) increased levodopa AUC (1.3-fold) and Cmax (1.2-fold) [11]. The bLF dose in this study was approximately 40-fold higher than that in the present study (14.6 mg/kg). Therefore, large doses may be required to be effective in humans. In this study, benserazide was used as the DCI; however, carbidopa is also an essential DCI formulation. In studies involving healthy individuals and PD patients, benserazide is known to increase Cmax and AUC compared with carbidopa [16]. In this study, benserazide, which has a stronger aromatic L-amino acid decarboxylase inhibitory effect, was used to evaluate the COMT inhibitory activity of bLF. As carbidopa was used in animal studies, the results may differ depending on the DCI used.