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Co-administration of budipine with levodopa increases dopamine levels Budipine, when used in combination with levodopa therapy in Parkinson's disease (PD), significantly increases dopamine levels in the brain. When administered to the nigra area in the brain, budipine caused a small rise in dopamine recovery in rats, but not in those pretreated with reserpine (the neurotoxicant used to induce PD symptoms), and alpha-methyl-p-tyrosine (alpha-MPT, used to limit dopamine synthesis from levodopa). However, when levodopa is administered to the nigra in reserpine-alpha-MPT-treated rats, dopamine levels are increased, and co-administration of budipine further enhances the levodopa-induced dopamine increase. Pretreating rats with budipine for 1 hour also significantly raised the activity of the enzyme L-aromatic amino acid decarboxylase (the enzyme used to convert levodopa to dopamine) in the striata and nigras of the intact rats, as well as in rats pretreated with reserpine alone. >From these results, the investigators concluded that the beneficial effects of budipine, when used as an adjunct to levodopa therapy of PD, may be due to an increase in the bioconversion of levodopa to dopamine. Source: Biggs CS, et al. Synapse 1998; 30(3): 309-317. Updated 19th November 1998 ---------------------------------------------------------------------------------------- Melatonin – a future treatment for Parkinson’s disease Melatonin may hold future possibilities for the treatment of Parkinson’s disease (PD), Alzheimer’s disease, stroke and neurotoxicity, due to its has anti-oxidant properties, and ability to penetrate the blood-brain barrier easily. Among an array of possible clinical benefits of the drug, melatonin is one of the most powerful scavengers of free radicals, which have been suggested as a possible cause of PD. An excess of free radicals produced in the substantia nigra of the brain causes tissue oxidation and progressive degenerative changes leading to PD. Bubeneik and colleagues, in this month’s issue of Biological Signals and Receptors, discuss the physiological merits of melatonin in a summary review of its clinical utilization. Bubenik et al. Biological Signals and Receptors 1998; 7(4): 195-219. Updated 23rd October 1998. -------------------------------------------------------------------------------------- New dopamine agonist shows superiour tolerability A recent study investigating the efficacy and tolerability of a new dopamine agonist, alpha-dihydroergocryptine (Almiridâ ), supported previous clinical trials reporting similar efficacy but superior tolerability in comparison with other dopamine agonists. Side effects were similar to those seen with other dopamine agonists. However, the incidence of severe psychiatric side reactions was low (3.2%). While increasing the daily dose of Almiridâ , the Webster score (used to measure efficacy) decreased from 15.9± 6.3 to 10.6± 6.2 points. In 45% of patients the severity of the disease improved according to the Hoehn and Yahr staging. This four-month observational study in 564 patients with idiopathic Parkinson's disease substantiated previous smaller clinical trials. Additional data concerning the tolerability of the drug should be obtained. Source: Jorg J. Aktuelle Neurologie 1998; 25(5): 198-201 -------------------------------------------------------------------------------------------- Under development: new transdermal patch for the treatment of Parkinson’s disease Schwarz Pharma (Mequon, USA) and Discovery Therapeutics, Inc. (DTI; Richmond, USA) recently announced an alliance to develop DTI’s novel dopamine agonist, N-0923, delivered in a transdermal patch for the treatment of Parkinson’s disease (PD). N-0923 will be administered to patients using a once-daily transdermal patch. "The patch revealed strong safety and efficacy features in a clinical phase II study," said Patrick Schwarz-Schütte, President and CEO of Schwarz Pharma AG. According to Dr Donald A McAfee, President and CEO of DTI, "This is a significant step in the treatment of PD, and we expect that this patch will provide patients with more consistent control of symptoms and fewer side-effects." Dr McAfee also noted that most patients with PD must take several medications each day to control symptoms, and the convenience of a once-a-day patch would be a welcomed improvement. Schwarz Pharma, Inc. is the US affiliate of Schwarz Pharma AG (Monheim, Germany), and will be responsible for completing development of the transdermal patch and for worldwide marketing, except in Japan. DTI was founded to invent, develop and commercialize pharmaceuticals for poorly met medical needs using novel signal molecule technologies, and developed the novel dopamine agonist for the treatment of PD. Source: Press Release, Mequon WI and Richmond VA, 3 August, 1998 --------------------------------------------------------------------------------------- Lazabemide hydrochloride: a potent new MAO-B inhibitor for the treatment of Parkinson’s disease Lazabemide hydrochloride (Tempium) is a new potent and selective MAO-B inhibitor, under development by F Hoffman La Roche Ltd. as a therapy for Parkinson’s disease (PD). Early studies have shown that when used as an adjuvant to levodopa, lazabemide hydrochloride may prevent dopaminergic neurotoxicity due to environmental toxins and/or free radicals, which are associated with the pathophysiology of PD. When assessed in 321 previously untreated patients with early-stage PD, lazabemide hydrochloride (25-200mg/day) reduced the risk of onset of disability requiring levodopa therapy by 51% compared with placebo after one year. In four out of every nine patients treated with a maintenance dose of lazabemide hydrochloride (37, 100, or 150mg/day), their dose of levodopa could be reduced. After one year, there was marked, moderate, and slight improvement in two, four, and three patients, respectively. A phase I trial with six volunteers showed that lazabemide hydrochloride (100-350mg po) was well tolerated and inhibited MAO-B for 16 and 36 hours at doses of 100 and 350mg taken twice daily, respectively. A Japanese approval application was made for lazabemide hydrochloride in late 1994 for PD, and a filing for approval in Alzheimer's disease as Tempium is expected in 1999. Lazabemide hydrochloride is in phase III clinical trials in Switzerland, preclinical trials in Italy, and also in Phase III trials for Alzheimer's disease and smoking cessation. Source: Pharmaprojects; PJB Publications Ltd, UK, 4 August 1998 -- Cheers , +----| Joao Paulo de Carvalho |------ + | [log in to unmask] | +--------| Salvador-Bahia-Brazil |------+