Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Treatment of On-Off Effect With A Dopa Decarboxylase Inhibitor

Treatment of On-Off Effect With A Dopa Decarboxylase Inhibitor Abstract Irregularities in motor response after continuing levodopa therapy of Parkinson disease (the "on-off effect") were assessed with the addition of l-α-methydopa hydrazine (carbidopa) in a doubleblind study. Thirteen of 20 patients improved while receiving carbidopa and levodopa while only four of 17 patients improved while receiving placebo and levodopa. Twenty-three of 37 patients improved in a subsequent non-blind trial of carbidopa plus levodopa. Improvement was not dependent on an increase in dose or frequency of levodopa administration. Adverse effects included dyskinesia, imbalance, and confusion; nausea was eliminated. One patient died of glomerulonephritis that predated the drug trial, but worsened progressively during and after it. Carbidopa's suppression of the "on-off effect" suggests that extracerebral factors may be important in this phenomenon. References 1. Barbeau A: Contributions of levodopa therapy to the neuropharmacology of akinesia , in Siegfried J (ed): Parkinson's Disease: Rigidity, Akinesia, Behavior . Bern, Hans Huber, 1972, vol 1, pp 152-174. 2. Sweet R, McDowell F: The "on-off" response to chronic L-DOPA treatment of parkinsonism . Adv Neurol 5:331-338, 1974. 3. Damasio AR, Castro-Caldas A, Levy A: The on-off effect . Adv Neurol 3:11-22, 1973. 4. Barbeau A: The clinical physiology of side effects in long-term L-DOPA therapy . Adv Neurol 5:347-366, 1974. 5. Ambani LM, Van Woert MA: Start hesitation: A side effect of long-term levodopa therapy . N Engl J Med 288:1113-1115, 1973.Crossref 6. Claveria LE, Calne DB, Allen JG: "On-off" phenomenon related to high plasma levodopa . Br Med J 2:641-643, 1973.Crossref 7. Tolosa ES, Martin WE, Cohen HP: Value of plasma-DOPA determinations in the management of Parkinson's disease . Lancet 1:942, 1973.Crossref 8. Fahn S: "On-off" phenomenon with levodopa therapy in parkinsonism . Neurology 24:431-441, 1974.Crossref 9. Sweet R, McDowell F: Plasma DOPA concentrations and the "on-off" effect after chronic treatment of Parkinson's disease . Neurology 24:953-956, 1974.Crossref 10. Tissot R, Bartholini G, Pletscher A: Druginduced changes in extracerebral dopa metabolism in man . Arch Neurol 20:187-190, 1969.Crossref 11. Papavasiliou PS, Cotzias GC, Duby SE, et al: Levodopa in parkinsonism: Potentiation of central effects with a peripheral inhibitor . N Engl J Med 286:8-14, 1972.Crossref 12. Chase TN, Wantanabe AM: Methyldopahydrazine as an adjunct to L-DOPA therapy in parkinsonism . Neurology 22:384-392, 1972.Crossref 13. Yahr M (ed): Treatment of parkinsonism: The role of DOPA decarboxylase inhibitors , in: Adv Neurol New York, Raven Press, 1973, vol 2. 14. McDowell F, Lee JE, Swift T, et al: Treatment of Parkinson's syndrome with L-dihydroxyphenylalanine (levodopa) . Ann Intern Med 72:29-35, 1970.Crossref 15. Lee J, Sweet R, McDowell F: Treatment of parkinsonism with levodopa: Follow-up after two years of treatment . Ann Intern Med 75:703-708, 1971.Crossref 16. Hoehn MM, Yahr MD: Parkinsonism: Onset, progression, and mortality . Neurology 17:427-442, 1967.Crossref 17. Muenter M, Tyce GM: L-DOPA therapy of Parkinson's disease: Plasma L-DOPA concentration, therapeutic response, and side effects . Mayo Clin Proc 46:231-239, 1971. 18. Papavasilious PS, Cotzias GC, Mena I: Short and long term approaches to the "on-off" phenomenon . Adv Neurol 5:379-386, 1974. 19. Mendez JS, Cotzias GC, Papavasiliou PS, et al: "On-off" phenomenon during treatment of parkinsonism with L-DOPA , in Yahr M (ed): Current Concepts in the Treatment of Parkinsonism . New York, Raven Press, 1974, pp 151-160. 20. Klawans H Jr: Stereotyped movements in guinea pigs after chronic administration of amphetamine, in Calne DB, Barbeau A, Chase TN (eds): Symposium on Dopamine Receptors. New York, Raven Press, to be published. 21. Barbeau A: High level levodopa therapy in Parkinson's disease: Five years later . Trans Am Neurol Assoc , to be published. 22. Sandler M: The dopa effect: Possible significance of transamination and tetrahydroisoquinoline formation . Adv Neurol 2:255-264, 1973. 23. Duby SE, Cotzias GC, Papavasiliou PS, et al: Injected apomorphine and orally administered levodopa in parkinsonism . Arch Neurol 27:474-480, 1972.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Treatment of On-Off Effect With A Dopa Decarboxylase Inhibitor

Loading next page...
 
/lp/american-medical-association/treatment-of-on-off-effect-with-a-dopa-decarboxylase-inhibitor-i4oocm5lP2
Publisher
American Medical Association
Copyright
Copyright © 1975 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1975.00490500080010
Publisher site
See Article on Publisher Site

Abstract

Abstract Irregularities in motor response after continuing levodopa therapy of Parkinson disease (the "on-off effect") were assessed with the addition of l-α-methydopa hydrazine (carbidopa) in a doubleblind study. Thirteen of 20 patients improved while receiving carbidopa and levodopa while only four of 17 patients improved while receiving placebo and levodopa. Twenty-three of 37 patients improved in a subsequent non-blind trial of carbidopa plus levodopa. Improvement was not dependent on an increase in dose or frequency of levodopa administration. Adverse effects included dyskinesia, imbalance, and confusion; nausea was eliminated. One patient died of glomerulonephritis that predated the drug trial, but worsened progressively during and after it. Carbidopa's suppression of the "on-off effect" suggests that extracerebral factors may be important in this phenomenon. References 1. Barbeau A: Contributions of levodopa therapy to the neuropharmacology of akinesia , in Siegfried J (ed): Parkinson's Disease: Rigidity, Akinesia, Behavior . Bern, Hans Huber, 1972, vol 1, pp 152-174. 2. Sweet R, McDowell F: The "on-off" response to chronic L-DOPA treatment of parkinsonism . Adv Neurol 5:331-338, 1974. 3. Damasio AR, Castro-Caldas A, Levy A: The on-off effect . Adv Neurol 3:11-22, 1973. 4. Barbeau A: The clinical physiology of side effects in long-term L-DOPA therapy . Adv Neurol 5:347-366, 1974. 5. Ambani LM, Van Woert MA: Start hesitation: A side effect of long-term levodopa therapy . N Engl J Med 288:1113-1115, 1973.Crossref 6. Claveria LE, Calne DB, Allen JG: "On-off" phenomenon related to high plasma levodopa . Br Med J 2:641-643, 1973.Crossref 7. Tolosa ES, Martin WE, Cohen HP: Value of plasma-DOPA determinations in the management of Parkinson's disease . Lancet 1:942, 1973.Crossref 8. Fahn S: "On-off" phenomenon with levodopa therapy in parkinsonism . Neurology 24:431-441, 1974.Crossref 9. Sweet R, McDowell F: Plasma DOPA concentrations and the "on-off" effect after chronic treatment of Parkinson's disease . Neurology 24:953-956, 1974.Crossref 10. Tissot R, Bartholini G, Pletscher A: Druginduced changes in extracerebral dopa metabolism in man . Arch Neurol 20:187-190, 1969.Crossref 11. Papavasiliou PS, Cotzias GC, Duby SE, et al: Levodopa in parkinsonism: Potentiation of central effects with a peripheral inhibitor . N Engl J Med 286:8-14, 1972.Crossref 12. Chase TN, Wantanabe AM: Methyldopahydrazine as an adjunct to L-DOPA therapy in parkinsonism . Neurology 22:384-392, 1972.Crossref 13. Yahr M (ed): Treatment of parkinsonism: The role of DOPA decarboxylase inhibitors , in: Adv Neurol New York, Raven Press, 1973, vol 2. 14. McDowell F, Lee JE, Swift T, et al: Treatment of Parkinson's syndrome with L-dihydroxyphenylalanine (levodopa) . Ann Intern Med 72:29-35, 1970.Crossref 15. Lee J, Sweet R, McDowell F: Treatment of parkinsonism with levodopa: Follow-up after two years of treatment . Ann Intern Med 75:703-708, 1971.Crossref 16. Hoehn MM, Yahr MD: Parkinsonism: Onset, progression, and mortality . Neurology 17:427-442, 1967.Crossref 17. Muenter M, Tyce GM: L-DOPA therapy of Parkinson's disease: Plasma L-DOPA concentration, therapeutic response, and side effects . Mayo Clin Proc 46:231-239, 1971. 18. Papavasilious PS, Cotzias GC, Mena I: Short and long term approaches to the "on-off" phenomenon . Adv Neurol 5:379-386, 1974. 19. Mendez JS, Cotzias GC, Papavasiliou PS, et al: "On-off" phenomenon during treatment of parkinsonism with L-DOPA , in Yahr M (ed): Current Concepts in the Treatment of Parkinsonism . New York, Raven Press, 1974, pp 151-160. 20. Klawans H Jr: Stereotyped movements in guinea pigs after chronic administration of amphetamine, in Calne DB, Barbeau A, Chase TN (eds): Symposium on Dopamine Receptors. New York, Raven Press, to be published. 21. Barbeau A: High level levodopa therapy in Parkinson's disease: Five years later . Trans Am Neurol Assoc , to be published. 22. Sandler M: The dopa effect: Possible significance of transamination and tetrahydroisoquinoline formation . Adv Neurol 2:255-264, 1973. 23. Duby SE, Cotzias GC, Papavasiliou PS, et al: Injected apomorphine and orally administered levodopa in parkinsonism . Arch Neurol 27:474-480, 1972.Crossref

Journal

Archives of NeurologyAmerican Medical Association

Published: Aug 1, 1975

References