Orally Active Carbamate Prodrugs of the Selective Dopamine Agonist N-0437: In-vivo Activities in the 6-OHDA Turning Model and In-vitro Activities

Daas, Izaak den; Boer, P. de; Tepper, Pieter G.; Rollema, Hans; Horn, Alan S.

doi:10.1111/j.2042-7158.1991.tb05439.x

Cited by 8 publications

(1 citation statement)

References 16 publications

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“…Furthermore the in-vivo activities of carbamate prodrugs of N-0437 were determined by examining the effects of the prodrugs, after their oral administration in rats with unilateral 6-OHDA lesions of the striatum. A comparison of the area under the curve of the time-effect curves of the prodrugs, revealed a significantly improved duration of action compared with N-0437 during the period 11-15 h after administration, for the propylcarbamate and the dimethoxyphenylcarbamate derivatives [ 78 , 79 ]. More recently the ( S )-enantiomer of compound N-0437 (rotigotine) has been formulated as a transdermal patch (NEUPRO ® ) [ 80 ].…”

Section: Dopamine Receptor Agonist Prodrugsmentioning

confidence: 99%

Antiparkinson Prodrugs

2008

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Parkinson’s disease (PD) is a progressive, neurodegenerative disorder which involves the loss of dopaminergic neurons of the substantia nigra pars compacta. Current therapy is essentially symptomatic, and L-Dopa (LD), the direct precursor of dopamine (DA), is the treatment of choice in more advanced stages of the disease. Substitution therapy with LD is, however, associated with a number of acute problems. The peripheral conversion of LD by amino acid decarboxylase (AADC) to DA is responsible for the typical gastrointestinal (nausea, emesis) and cardiovascular (arrhythmia, hypotension) side effects. To minimize the conversion to DA outside the central nervous system (CNS) LD is usually given in combination with peripheral inhibitors of AADC (carbidopa and benserazide). In spite of that, other central nervous side effects such as dyskinesia, on-off phenomenon and end-of-dose deterioration still remain. The main factors responsible for the poor bioavailability and the wide range of inter- and intra-patient variations of plasma levels are the drug’s physical-chemical properties: low water and lipid solubility, resulting in unfavourable partition, and the high susceptibility to chemical and enzymatic degradation. In order to improve the bioavailability, the prodrug approach appeared to be the most promising and some LD prodrugs have been prepared in an effort to solve these problems. We report here a review of progress in antiparkinson prodrugs, focusing on chemical structures mainly related to LD, DA and dopaminergic agonists.

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Section: Dopamine Receptor Agonist Prodrugsmentioning

confidence: 99%

Antiparkinson Prodrugs

2008

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Risks of reusing coronary angioplasty catheters: Results of an experimental study

Grimandi

Sellal²,

Grimandi³

et al. 1996

Cathet. Cardiovasc. Diagn.

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This experimental study was conducted to evaluate the microbiological and mechanical risks of reusing angioplasty catheters after decontamination and resterilization. The catheters studied were decontaminated in an ultrasound chamber, rinsed, dried, wrapped, and resterilized at 25 or 35 Kgray. Sterility checks performed on catheters cut into three segments concerned bacteria, mushrooms, yeasts, and pyrogens. The surface condition of the balloons was studied by scanning electron microscopy. The mechanical properties analyzed were balloon diameter and bursting pressure and the mean resistance of the catheter body to breakage. Seventy angioplasty catheters of three different types (rapid exchange, coaxial, and on‐wire balloon catheter) were tested. Decontamination proved insufficient owing to the persistance of cellular elements on the balloon surface and the presence of pyrogens. Sterility of the material was not ensured with an irradiation of 25 Kgray. It was probable but not certain with 35 Kgray, since an inhibitory effect on microorganism growth was noted. Mechanical properties were not modified significantly. Our results do not favor the reuse of coronary angioplasty catheters. Better decontamination is desirable but difficult to obtain because of the adhesion of cellular elements to the polymers composing the catheters. Although our results are not necessarily applicable to all resterilization protocols, they indicate that teams desiring to reuse angioplasty material should first test the validity of their procedure for decontamination and resterilization. © 1996 Wiley‐Liss, Inc.

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Metabolic Considerations in Prodrug Design

Balant

2003

Burger's Medicinal Chemistry and Drug Discovery

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This review concentrates on prodrugs designed by pharmaceutical chemists to overcome biopharmaceutical or pharmacokinetic (essentially metabolic) problems encountered with active principles. The investigations presented in this review illustrate the types of problems pharmaceutical chemists have tried to solve and the metabolic, kinetic, or biopharmaceutical rationale behind these attempts. Although very little published information is available on pharmacokinetic methods useful in the study of prodrugs and on the regulatory requirements needed for prodrug development, the authors have tried to develop some general ideas that might be useful in this regard.

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Orally Active Carbamate Prodrugs of the Selective Dopamine Agonist N-0437: In-vivo Activities in the 6-OHDA Turning Model and In-vitro Activities

Cited by 8 publications

References 16 publications

Antiparkinson Prodrugs

Antiparkinson Prodrugs

Risks of reusing coronary angioplasty catheters: Results of an experimental study

Metabolic Considerations in Prodrug Design

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