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hi syber-siblings there have been a few questions about tolcapone/tasmar recently so i couldn't resist going out hunting janet --------------------------------------------------------------------- ABSTRACT - KURTH ET AL - JANUARY 1997 --------------------------------------------------------------------- Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson's disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Tolcapone Fluctuator Study Group I. --------------------------------------------------------------------- Tolcapone is a potent catechol-O-methyltransferase inhibitor that prolongs the plasma half-life of levodopa. This multicenter, double-blind, placebo-controlled study used two 10-hour clinical evaluations to compare the efficacy and safety of three doses of tolcapone (50, 200, and 400 mg tid) with placebo in patients with Parkinson's disease (PD) experiencing motor fluctuations from levodopa/carbidopa. One hundred fifty-one patients completed the study. Clinical evaluations lasting 10 hours were performed on day -1 and day 42 using United Parkinson's Disease Rating Scale motor subscale and "on/off" and dyskinesia assessments every 30 minutes. Tolcapone significantly reduced "off" time an average of 40% and increased total "on" time by about 25% at all dose levels, as compared to placebo treatment. Levodopa/carbidopa dosage and frequency were significantly reduced. Tolcapone was well tolerated, with patients experiencing typical dopaminergic side effects that could be reduced or eliminated by lowering levodopa/carbidopa dosages. Tolcapone was effective at prolonging the clinical benefit of levodopa and reducing total levodopa requirements in PD patients with motor fluctuations. Neurology 1997 Jan;48(1):81-87 Kurth MC, Adler CH, Hilaire MS, Singer C, Waters C, LeWitt P, Chernik DA, Dorflinger EE, Yoo K Barrow Neurological Institute, Phoenix, AZ 85013, USA. PMID: 9008498, MUID: 97161241 --------------------------------------------------------------------- NEWS - REUTERS - JANUARY 1997 --------------------------------------------------------------------- New Parkinson's Disease Treatment --------------------------------------------------------------------- NEW YORK, Jan 21 (Reuters) -- A new drug may allow people with Parkinson's disease to live each day on a more even keel, with fewer fluctuations in their symptoms, according to researchers. Patients with the disorder also need less of the main medication for Parkinson's -- levodopa -- when the drug tolcapone is added to their treatment. The new drug works by slowing the metabolism, or break down, of levodopa, thus prolonging its availability to the body. "This is an important development in the treatment of Parkinson's disease," says Dr. Mathias Kurth, a neurologist with Barrow Neurological Institute in Phoenix, Arizona. "This is another step toward making treatment better and smoother and making life better for patients," he adds. The Barrow Neurological Institute is one of several medical centers around the nation involved in the Tolcapone Fluctuation Study Group. Others include the Mayo Clinic, Scottsdale, Arizona; Boston University, Boston, Massachusetts; the University of Miami, Florida; the University of Southern California, Los Angeles; and Sinai Hospital of Detroit, Michigan. The study included 151 Parkinson's patients who each day experienced "off" periods of muscle slowness, rigidity, and trembling of the arms and legs, and "on" periods of relatively normal functioning when their levodopa dosage was working. In a report published in January's issue of Neurology, the researchers note that tolcapone reduced patients' "off" time by an average of 40% and increased their total "on" time by about 25%. Patients taking tolcapone also needed fewer doses of levodopa. Neurologists have known for some time that levodopa works well when it is first given to Parkinson's patients. The drug is converted by the body into dopamine, a nerve transmitter substance that reduces muscle tone so that movement is not jerky. In Parkinson's patients, dopamine levels are diminished in the parts of the brain -- collectively known as the basal ganglia -- affected by the disease. But after a time, the beneficial effects of levodopa often suddenly wear off, and other drugs must be given as substitutes. According to the researchers, tolcapone prolongs the effect of levodopa by blocking an enzyme that breaks down and converts levodopa to an inactive substance. This allows levodopa to remain in the bloodstream longer. Side effects of tolcapone observed in the study include nausea and abnormal muscle movements (uncontrollable twitches and jerks). But the researchers note these can be lessened or eliminated by adjusting the dose of levodopa. Tolcapone's maker is Hoffman-La Roche, of Nutley, New Jersey. The drug company expects to obtain Food and Drug Administration approval for tolcapone some time this year. According to the American Academy of Neurology in Minneapolis, Parkinson's disease affects more than 800,000 people in the U.S., with about 50,000 new cases diagnosed each year. SOURCE: Neurology (1997;48:81-87) Copyright 997 Reuters Limited. <http://www.reutershealth.com/news/rhdn/199701/1997012104.html> --------------------------------------------------------------------- AMERICAN ACADEMY OF NEUROLOGY - ADLER ET AL - APRIL 1997 --------------------------------------------------------------------- New Drug Improves On-Off Periods in PD April 17, 1997 --------------------------------------------------------------------- Clinical results presented at the American Academy of Neurology annual meeting in Boston indicate that tolcapone (Tasmar, Roche) is effective in patients with Parkinson's disease suffering from on-off periods. Tolcapone is the most potent and selective inhibitor of COMT, the enzyme that metabolizes levodopa peripherally, discovered to date. In a double-blind, placebo-controlled trial of 215 patients, Adler et al. found that tolcapone reduced off periods by 30-37%, even as daily levodopa requirements were reduced by 36-46%. Tolcapone was well tolerated, with only 3-5% of patients withdrawing from the study because of adverse effects. Study results are similar to those reported in the Jan. Neurology (1997; 48: 81-7). <http://pharminfo.com/pubs/pnn/pnn9.html#8> ------------------------------------------------------------------------------ ABSTRACT - YAMAMOTO ET AL - 1997 ------------------------------------------------------------------------------ Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease. ------------------------------------------------------------------------------ The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 time points before and after the chronic administration of tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved at all points of determination. Eight patients with wearing-off phenomenon on levodopa showed symptomatic improvement on the combination. The area under the curve (AUC) for levodopa increased by 34% (p = 0.0059) after the administration of tolcapone. The elimination half-life (T1/2) of levodopa was significantly prolonged by 81% (p = 0.0001) after the treatment. The AUC of 3-O-methyldopa, a metabolite of levodopa, was decreased by 79% (p = 0.0001) and the Cmax (maximum concentration) was also decreased by 80%d after the administration (p = 0.0001) of tolcapone. The combination of tolcapone and levodopa was well tolerated. Our findings suggest that tolcapone improves the pharmacokinetics of levodopa in plasma and motor symptoms of fluctuating PD patients. It is suggested that tolcapone may be useful drug adjunct to levodopa in treating patients with PD J Neural Transm 1997;104(2-3):229-236 Yamamoto M, Yokochi M, Kuno S, Hattori Y, Tsukamoto Y, Narabayashi H, Tohgi H, Mizuno Y, Kowa H, Yanagisawa N, Kanazawa I Department of Neurology, Kagawa Prefectural Central Hospital, Japan. PMID: 9203084, MUID: 97346667 ----------------------------------------------------------------------- [log in to unmask]