Disease relevance of Modopar

• Implications of combined treatment with 'Madopar' and L-deprenil in Parkinson's disease. A long-term study [1].
• End-of-dose failure, which had developed in 4 patients, and peak-dose dyskinesias present in 6 patients during treatment with standard Madopar, improved significantly with Sinemet CR [2].
• The therapeutic efficacy of Madopar HBS was investigated in 5 patients with advanced parkinsonism [3].

Psychiatry related information on Modopar

• 3-O-methyldopa attenuates the effects of Madopar on the haloperidol-induced cataleptic behavior and the locomotor activity in the mouse [4].
• The effects of 3 mg haloperidol and 125 mg Madopar on duration discrimination (DD) as well as reaction times were tested in a placebo-controlled, double-blind crossover study with 24 healthy male volunteers [5].

High impact information on Modopar

• Clinically, Sinemet and Madopar were similar; however, DOPA levels were higher, but with a shorter half-life, on Madopar [6].
• Growth hormone and prolactin stimulation by Madopar in Parkinson's disease [7].
• In 3 patients with longstanding Parkinson's disease treated with Madopar or Nacom, who were not included in the study, the doses of the above drugs could be maintained or reduced by addition of deprenyl [8].
• The relative bioavailability (Madopar DR vs. Madopar HBS) was 1.73 on day 1 and 1.32 on day 8 [9].
• In conclusion, the observed differences in C(max), t(max) and AUC are consistent with a faster rate and higher extent of levodopa absorption after administration of Madopar DR [9].

Chemical compound and disease context of Modopar

• Therapeutic responses to Sinemet CR were studied in 37 patients with early Parkinson's disease previously treated with standard (Madopar) or controlled-release (Madopar HBS) levodopa/benserazide combinations [2].
• The efficacy and tolerance of treatment with an 8-alpha-amino-ergoline derivative CU32-o85, Mesulergine, were compared with levodopa/benserazide (Madopar) in a 3 month double-blind controlled trial in 31 patients with Parkinson's disease, not previously treated with levodopa [10].
• Twenty patients with paralysis agitans took part in a double-blind, cross-over investigation of CB 154 (2-bromo-alpha-ergocryptine) and Madopar (L-Dopa + benserazid (a peripheral decarboxylase inhibitor), dose ratio 4:1) [11].

Biological context of Modopar

• The mean relative bioavailability (versus standard Madopar) was 58 and 67% (value normalized to dose) for one and two HBS capsules, respectively [12].
• Single-dose pharmacokinetics of Madopar HBS in patients and effect of food and antacid on the absorption of Madopar HBS in volunteers [13].

Anatomical context of Modopar

• 4. Parkinsonian patients who died during Madopar therapy demonstrated a significant increase of MHPG in caudate n., putamen, s. nigra, n. ruber, n. amygdalae and n. accumbens when compared to the untreated group, indicating an enhanced turnover of noradrenaline in these areas [14].

Associations of Modopar with other chemical compounds

• Bioavailability of L-dopa after Madopar HBS administration in healthy volunteers [12].
• Inhibition of decarboxylase and levels of dopa and 3-O-methyldopa: a comparative study of benserazide versus carbidopa in rodents and of Madopar standard versus Madopar HBS in volunteers [15].
• In an open, uncontrolled study the longterm (9 years) effect of treatment with Madopar alone (n = 377) or in combination with l-deprenyl (selegiline, selective monoamine oxidase type B inhibitor) (n = 564) have been compared in Parkinsonian patients [16].
• In patients treated with L-dopa plus benserazide or carbidopa (Madopar or Sinemnet), however, plasma SSAO activity is strongly inhibited, contrary to the paradoxical 3-fold increase in plasma aromatic-L-amino acid decarboxylase activity we reported previously [17].
• In patients on Madopar therapy the TSH and Prl responses to TRH were greater than in unmedicated patients and comparable to those of controls, while in patients on Sinemet therapy the pituitary responses were undistinguishable from those of unmedicated subjects [18].

Gene context of Modopar

• Madopar, depending on the dose regimen, markedly antagonized the haloperidol-induced catalepsy [4].
• Pretreatment with a new selective catechol-O-methyltransferase (COMT) inhibitor, tolcapone (30 mg/kg p.o.), slightly potentiated the antagonistic effect of Madopar (15 mg/kg p.o.) on haloperidol-induced catalepsy [19].

Analytical, diagnostic and therapeutic context of Modopar

• In a longitudinal study of three patients started on Madopar treatment the induction of plasma ALAAD was found to occur gradually over 3-4 weeks [20].
• In an open-label, two-way cross-over study, 20 healthy volunteers were randomized to receive first either Madopar DR or Madopar HBS for 8 days [9].
• The accuracy of the procedure and the absence of interference from excipients were confirmed by the good agreement in the results for the assay of several batches of Madopar capsules and one of Madopar tablets with those obtained by the manufacturer by an HPLC procedure [21].
• The ability of 3OMD to significantly inhibit Madopar effects was observed in the locomotor testing paradigm; the locomotor hyperactivity in Madopar-treated animals was significantly inhibited by a prior intraperitoneal injection of 3OMD [4].
• In this Danish-Norwegian randomized double-blind parallel-group multicentre study, we compared the therapeutic response of slow-release Madopar HBS to standard Madopar in 134 de novo patients with idiopathic Parkinson's disease during a 5-year period [22].

References