Clinical implications of irregular ADMET properties with levodopa and other antiparkinson's drugs

Dézsi, Lívia; Vécsei, László

doi:10.1517/17425255.2014.878702

Cited by 12 publications

(10 citation statements)

References 102 publications

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“…These responses are also related to individual profile differences in the absorption, distribution, metabolism, excretion, and toxicity of the drugs. 24 , 25 , 58 , 59 For example, L 1 causes an increase in iron excretion exclusively in the urine, DFX exclusively in the feces, and DFO mostly in the urine and also the feces ( Table 3 ). 14 , 24 , 25 , 59…”

Section: Clinical Use and Efficacy Of Deferoxamine Deferiprone And mentioning

confidence: 99%

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

Kontoghiorghe¹,

Kontoghiorghes²

2016

DDDT

131

152

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The prevalence rate of thalassemia, which is endemic in Southeast Asia, the Middle East, and the Mediterranean, exceeds 100,000 live births per year. There are many genetic variants in thalassemia with different pathological severity, ranging from a mild and asymptomatic anemia to life-threatening clinical effects, requiring lifelong treatment, such as regular transfusions in thalassemia major (TM). Some of the thalassemias are non-transfusion-dependent, including many thalassemia intermedia (TI) variants, where iron overload is caused by chronic increase in iron absorption due to ineffective erythropoiesis. Many TI patients receive occasional transfusions. The rate of iron overloading in TI is much slower in comparison to TM patients. Iron toxicity in TI is usually manifested by the age of 30–40 years, and in TM by the age of 10 years. Subcutaneous deferoxamine (DFO), oral deferiprone (L1), and DFO–L1 combinations have been effectively used for more than 20 years for the treatment of iron overload in TM and TI patients, causing a significant reduction in morbidity and mortality. Selected protocols using DFO, L1, and their combination can be designed for personalized chelation therapy in TI, which can effectively and safely remove all the excess toxic iron and prevent cardiac, liver, and other organ damage. Both L1 and DF could also prevent iron absorption. The new oral chelator deferasirox (DFX) increases iron excretion and decreases liver iron in TM and TI. There are drawbacks in the use of DFX in TI, such as limitations related to dose, toxicity, and cost, iron load of the patients, and ineffective removal of excess iron from the heart. Furthermore, DFX appears to increase iron and other toxic metal absorption. Future treatments of TI and related iron-loading conditions could involve the use of the iron-chelating drugs and other drug combinations not only for increasing iron excretion but also for preventing iron absorption.

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Section: Clinical Use and Efficacy Of Deferoxamine Deferiprone And mentioning

confidence: 99%

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

Kontoghiorghe¹,

Kontoghiorghes²

2016

DDDT

131

152

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“…For instance, L-DOPA is usually administered in combination with carbidopa, which is well known to exacerbate nausea [13]. In the periphery, carbidopa prevents the conversion of L-DOPA to DA, and as its half-life exceeds that of L-DOPA, one might theoretically expect residual effects of carbidopa outside the CNS [202]. This treatment might well prevent the conversion of endogenous peripheral L-DOPA in addition to the exogenous L-DOPA that is concomitantly administrated.…”

Section: Therapeutic Approaches To Gi Symptomsmentioning

confidence: 99%

“…Therefore, the potential impact of carbidopa on peripheral organs involved in NMS deserves careful evaluation. This concept may be of importance when considering the administration of L-DOPA by intestinal gel infusion, which may act directly on GI tract [202]. …”

Section: Therapeutic Approaches To Gi Symptomsmentioning

confidence: 99%

Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments

Poirier

Aubé

Côté

et al. 2016

Parkinson's Disease

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A diagnosis of Parkinson's disease is classically established after the manifestation of motor symptoms such as rigidity, bradykinesia, and tremor. However, a growing body of evidence supports the hypothesis that nonmotor symptoms, especially gastrointestinal dysfunctions, could be considered as early biomarkers since they are ubiquitously found among confirmed patients and occur much earlier than their motor manifestations. According to Braak's hypothesis, the disease is postulated to originate in the intestine and then spread to the brain via the vagus nerve, a phenomenon that would involve other neuronal types than the well-established dopaminergic population. It has therefore been proposed that peripheral nondopaminergic impairments might precede the alteration of dopaminergic neurons in the central nervous system and, ultimately, the emergence of motor symptoms. Considering the growing interest in the gut-brain axis in Parkinson's disease, this review aims at providing a comprehensive picture of the multiple gastrointestinal features of the disease, along with the therapeutic approaches used to reduce their burden. Moreover, we highlight the importance of gastrointestinal symptoms with respect to the patients' responses towards medical treatments and discuss the various possible adverse interactions that can potentially occur, which are still poorly understood.

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“…Pulsatile stimulation, due to the short half-life and rapid catabolism of DA, leads to intermittent delivery to receptors [ 17 ]. It is suggested that continuous DAergic stimulation may delay or even reverse the motor complications [ 14 , 18 ].…”

Section: Symptomatic Treatments Of Parkinson’s Diseasementioning

confidence: 99%

Current Pharmaceutical Treatments and Alternative Therapies of Parkinson's Disease

Dong

Cui

2016

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Over the decades, pharmaceutical treatments, particularly dopaminergic (DAergic) drugs have been considered as the main therapy against motor symptoms of Parkinson's disease (PD). It is proposed that DAergic drugs in combination with other medications, such as monoamine oxidase type B inhibitors, catechol-O-methyl transferase inhibitors, anticholinergics and other newly developed non-DAergic drugs can make a better control of motor symptoms or alleviate levodopa-induced motor complications. Moreover, non-motor symptoms of PD, such as cognitive, neuropsychiatric, sleep, autonomic and sensory disturbances caused by intrinsic PD pathology or drug-induced side effects, are gaining increasing attention and urgently need to be taken care of due to their impact on quality of life. Currently, neuroprotective therapies have been investigated extensively in pre-clinical studies, and some of them have been subjected to clinical trials. Furthermore, non-pharmaceutical treatments, including deep brain stimulation (DBS), gene therapy, cell replacement therapy and some complementary managements, such as Tai chi, Yoga, traditional herbs and molecular targeted therapies have also been considered as effective alternative therapies to classical pharmaceutics. This review will provide us updated information regarding the current drugs and non-drugs therapies for PD.

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Clinical implications of irregular ADMET properties with levodopa and other antiparkinson's drugs

Cited by 12 publications

References 102 publications

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

Efficacy and safety of iron-chelation therapy with deferoxamine, deferiprone, and deferasirox for the treatment of iron-loaded patients with non-transfusion-dependent thalassemia syndromes

Gastrointestinal Dysfunctions in Parkinson’s Disease: Symptoms and Treatments

Current Pharmaceutical Treatments and Alternative Therapies of Parkinson's Disease

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