Deuterium-substituted L-DOPA displays increased behavioral potency and dopamine output in an animal model of Parkinson's disease: comparison with the effects produced by L-DOPA and an MAO-B inhibitor.

The most effective treatment of Parkinson's disease (PD) L-DOPA is associated with major side effects, in particular L-DOPA-induced dyskinesia, which motivates development of new treatment strategies. We have previously shown that chronic treatment with a substantially lower dose of deuterium-substituted L-DOPA (D3-L-DOPA), compared with L-DOPA, produced equal anti-parkinsonian effect and reduced dyskinesia in 6-OHDA-lesioned rats. The advantageous effects of D3-L-DOPA are in all probability related to a reduced metabolism of deuterium dopamine by the enzyme monoamine oxidase (MAO).

Cardiovascular effects, pharmacokinetics and cross-reactivity in digitalis glycoside immunoassays of an antidiarrheal uzara root extract.

Uzara glycosides (UG) extracted from Xysmalobium undulatum are used for treating non-specific diarrhea.Cross-reactivity has been described for UG in digitalis glycoside assays but digitalis-like cardiac effects are controversially discussed. Therefore, we performed a randomized, singleblind cross-over study in 18 healthy volunteers receiving a commercially available Uzara product (Uzara® Lösung N, Stada AG, Bad Vilbel, Germany (ULN)), digoxin (1 mg, i.

Deuterium substitutions in the L-DOPA molecule improve its anti-akinetic potency without increasing dyskinesias.

Treatment of Parkinson's disease is complicated by a high incidence of L-DOPA-induced dyskinesias (LID). Strategies to prevent the development of LID aim at providing more stable dopaminergic stimulation. We have previously shown that deuterium substitutions in the L-DOPA molecule (D3-L-DOPA) yield dopamine that appears more resistant to enzymatic breakdown.

Synergistic effects of deuterium oxide and gemcitabine in human pancreatic cancer cell lines.

Purpose: Pancreatic cancer still remains a treatment-refractory cancer. Standard therapy for metastatic cancer is gemcitabine (dFdC) chemotherapy. Since heavy water (deuterium oxide, D2O) was shown to be active in pancreatic cancer in vitro, we examined the simultaneous or sequential cytotoxic effects of D2O and dFdC in pancreatic cancer cell lines (AsPC-1, BxPC-3, and PANC-1).

Changed phosphodiesterase selectivity and enhanced in vitro efficacy by selective deuteration of sildenafil.

In order to explore whether selective deuteration of sildenafil affects selectivity and efficacy of the drug, the inhibitory activity of sildenafil (1-[4-ethoxy-3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)phenyl-sulfonyl] -4-methylpiperazine citrate, CAS 139755-83-2) and three deuterated sildenafil derivatives, D8-piperazine-sildenafil (BDD-10402), D3-methyl-D8-piperazine-sildenafil (BDD-10403) and D5-ethoxy-Sildenafil (BDD-10406) against phosphodiesterases 1-6 was compared. Furthermore, the relaxant effect of sildenafil and its deuterated derivatives in a contractility assay on rabbit corpus cavernosum strips from New Zealand rabbits was investigated. BDD-10406 exhibits a 2-fold higher selectivity for phosphodiesterase 5 versus phosphodiesterase 6 than sildenafil.