Influence of the dopamine agonist alpha-dihydroergocryptine on the pharmacokinetics of levodopa in patients with Parkinson's disease

This study investigated whether chronic coadministration of alpha -dihydroergocryptine (DHEC) altered the plasma pharmacokinetics of individualized treatments with levodopa in 12 patients with Parkinson's disease. Steady-state pharmacokinetics of plasma levodopa (L-Dopa) under combined treatment were compared with those under treatment with L-Dopa alone. There was no evidence of increased exposure to L-Dopa caused by concomitant treatment with DHEC. In contrast, additional treatment with DHEC reduced the overall exposure to L-Dopa (17.5% reduction in area under the curve; 95% Cl: 23%-6%). This effect was small but statistically significant for the area under the plasma concentration-time curve, whereas t(max) (time of maximum plasma concentration) and peak-to-trough fluctuation were not affected. C-max (maximum plasma concentration), on average, was reduced to a similar extent (-14.5%; 95% Cl: 38% to -17%), albeit not significantly. The magnitude of the interaction does not suggest changing the current clinical practice of up-titrating DHEC and subsequently adapting L-Dopa to the individual needs of patients

Bis(tetramethylcyclopentadienyl)titanium chemistry. Molecular structures of [(C(5)HMe(4))(mu-eta(1): eta(5)-C(5)Me(4))Ti](2) and [(C(5)HMe(4))(2)Ti]N-2(2)

Thermolysis of bis(tetramethylcyclopentadienyl)-stabilized titanium(III) compounds (C(5)HMe(4))(2)TiR (R = Me (2), Ph (3)) yields, in marked contrast with the bis(pentamethylcyclopentadienyl) analog, the dimeric product [(C(5)HMe(4))(mu-eta(1):eta(5)-C(5)Me(4))Ti](2) (4), With a bridging metalated tetramethylcyclopentadienyl ligand. The hydride (C(5)HMe(4))(2)TiH (5), synthesized by hydrogenolysis of 2 or 3, reacts with N-2 to form the dinuclear Ti(II) dinitrogen compound [(C(5)HMe(4))(2)Ti]N-2(2) (8) Under a dynamic vacuum, the dinitrogen complex 8 loses the N-2 ligand to give the titanocene (C(5)HMe(4))(2)Ti (10). The molecular structures of both 4 and 8 were determined by X-ray diffraction methods

Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits

N-methyl-D-aspartate receptor (NMDAR) composition in granule cells changes characteristically during cerebellar development. To analyze the importance of NR2B replacement by NR2C and NR2A subunits until the end of the first month of age, we generated mice with lasting NR2B expression but deficiency for NR2C (NR2C-2B mice). Mutant phenotype was different from NR2C knock-out mice as loss of granule cells and morphological changes in NR2C/2B cerebellar architecture were already evident from the second postnatal week. Increased NR2B subunit levels led also to a gradual down-regulation of cerebellar NR2A levels, preceding the development of motor impairment in adult animals. Therefore, cerebellar NR2A is important for proper motor coordination and cannot be replaced by long-term expression of NR2B. Consequently, the physiological exchange of NMDA receptor subunits during cerebellar granule cell maturation is important for accurate postnatal development and function. (C) 2004 Elsevier Inc. All rights reserved