Summary
Basic aspects and recent advances in the understanding of the pharmacological mechanism of action of the clinically most used antiparkinson drugs are reviewed. Recent human and animal biochemical investigations clearly confirm and extend previous findings indicating that benserazide is much more potent than carbidopa as peripheral decarboxylase inhibitor. L-DOPA in combination with benserazide or carbidopa constitutes the best available therapy for Parkinson's disease (PD). To reduce peaks and rapid fluctuations of L-DOPA plasma levels (possibly responsible for peak-dose dyskinesias and end-of-dose deterioration) a slow-release formulation of L-DOPA in combination with benserazide or with benserazide plus catechol-O-methyltransferase inhibitors should be developed. In parkinsonian patients under long-term L-DOPA therapy monoamine oxidase inhibitors type B (MAO-B) e.g. (−)-deprenyl and firect dopamine receptor agonists (bromocriptine, lisuride, pergolide etc.), due to their L-DOPA-sparing effects, alleviate in some cases L-DOPA-induced side-effects e.g. dyskinesias and on-off phenomena. However, since (−)-deprenylm, due to its metabolism to (−)methamphetamine and (−)amphetamine, seem to have indirect sympathomimetic activity, new selective MAO-B inhibitors devoid of indirect sympathomimetic effects should be tested clinically to assess the functional role of pure MAO-B inhibition in the therapy of PD. The auxiliary therapy with direct dopmaine receptor agonists of the D-2 subtype represents another valid approach which should be further investigated in order to find novel dopamine agonists, less expensive than bromocriptine and strictly selective for D-2 receptor sites.
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References
Andén, N.E., and Grabowska, M., Pharmacological evidence for a stimulation of dopamine neurons by noradrenaline neurons in brain. Eur. J. Pharmac.39 (1976) 275–282.
Barbeau, A., Murphy, G.F., and Sourkes, T.L., Excretion of dopamine in diseases of basal ganglia. Science133 (1961) 1706.
Barbeau, A., L-DOPA therapy in Parkinson's disease. A critical review of nine years experience. Can. med. Ass. J.101 (1969) 58–89.
Barbeau, A., The clinical physiology of side effects in long-term L-DOPA therapy. Adv. Neurol.5 (1974) 347–365.
Barbeau, A., and Ry, M, Six-year results of treatment with levodopa plus benserazide in Parkinson's disease. Neurology (Minneap.)26 (1976) 399–404.
Bartholini, G., Burkard, W.P., Pletscher, A., and Bates, H.M., Increase of cerebral catecholamines caused by 3,4-dihydroxyphenylalanine after inhibition of peripheral decarboxylase. Nature215 (1967) 852–853.
Bartholini, G., and Pletscher, A., Effect of various decarboxylase inhibitors on the cerebral metabolism of dihydroxyphenylaline. J. Pharm. Pharmac.21 (1969) 323–324.
Bartholini, G., and Pletscher, A., Decarboxylase inhibitors. Pharmac. Thera. B1 (1975) 407–421.
Birkmayer, W., Long-term treatment with L-deprenyl. J. neural. Transm.43 (1978) 239–244.
Birkmayer, W., Danielczyk, W., and Riederer, P., Symptoms and side effects in the course of Parkinson's disease. J. nrural Transm., suppl.19 (1983) 185–199.
Birkmayer, W., and Hornykiewicz, O., Der L-Dihydroxy-phenylalanin (L-DOPA)-Effekt bei Parkinson-Akinesie. Wien. klin. Wschr.73 (1961) 787.
Birkmayer, W., Linauer, W., and Mentasti, M., Traitement à la L-Dopa combinée avec un inhibiteur de la décarboxylase (Ro 4-4602), in Monoamines, Noyaux gris centraux et syndrome de Parkinson, pp 435–441. Eds J. de Ajuriaguerra and G. Gauthier Symposium Bel-Air IV. Georg & Cie, Genève 1971.
Birkmayer, W., and Mentasti, M., Weitere experimentelle Untersuchungen über den Katecholaminstoffwechsel bei extrapyramidalen Erkrankungen (Parkinson- und Chorea-Syndrom). Arch. Psychiat. NervKrankh.210 (1967) 29–35.
Birkmayer, W., Riederer, P., Linauer, W., and Knoll, J., L-Deprenyl plus L-phenyalanine in the treatment of depression. J. neural Transm.59 (1984) 81–87.
Birkmayer, W., Riederer, P., Ambrosi, L., and Youdim, M.B.H., Implications of combined treatment with Madopar and L-deprenyl in Parkinson's disease. Lancet1 (1977) 59–63.
Birkmayer, W., Riederer, P., Youdim, M.B.H., and Linauer, W., The potentiation of the anti-akinetic effect after L-Dopa treatment by an IMAO-B, deprenyl. J. neural Transm.36 (1975) 303–326.
Burkard, W.P., Gey, K.F., and Pletscher, A., Inhibition of decarboxylase of aromatic aminoacids by 2, 3, 4-trihydroxybenzylhydrazine and its seryl derivative. Archs Biochem.107 (1964) 187–196.
Buu, N.T., Kuchel, O., and Parent, M.T., Competitive inhibition of catechol-O-methyltransferase by Ro 4-4602. Can. J. Biochem.55 (1977) 771–773.
Calne, D.B., Reid, J.L., and Vakil, S.D., Idiopathic parkinsonism treated with an extracerebral decarboxylase inhibitor in combination with levodopa. Br. med. J.3 (1971) 729–732.
Calne, D.B., Williams, A.C., Neophytides, A., Plotkin, C., Nutt, J.G., and Teychenne, P.F., Long-term treatment of Parkinsonism with bromocriptine. Lancet1 (1978) 735–738.
Calne, D.B., Clinical relevance of dopamine receptor classification. Trends Pharmac. Sci.3 (1980) 412–414.
Cohen, G., The pathobiology of Parkinson's disease: biochemical aspects of dopamine neuron senescence. J. neural Transm., suppl.19 (1983) 89–103.
Corrodi, H., Fuxe, K., Hökfelt, T., Lidbrink, P., and Ungerstedt, U., Effects of ergot drugs on central catecholamine neurons: evidence for a stimulation of central dopamine neurons. J. Pharm. Pharmac.25 (1973) 409–412.
Corrodi, H., Farnebo, L.O., Fuxe, K., and Hamberger, B., Effect of ergot drugs on central 5-hydroxytryptamine neurons: evidence for 5-hydroxytryptamine release or 5-hydroxytryptamine receptor stimulation. Eur. J. Pharmac.30 (1975) 172–181.
Cotzias, G.C., van Voert, M.H., and Schiffer, L.M., Aromatic aminoacids and modification of Parkinsonism. N. Engl. J. Med.276 (1967) 374.
Cotzias, G.C., Papavasiliou, P.S., and Gelline, R., Modification of Parkinsonism: chronic treatment with L-DOPA. N. Engl. J. Med.280 (1969) 337–345.
Creese, I., Dopamine receptors explained. Trends Neurosci.5 (1982) 40–43.
Csanda, E., Antal, J., Antony, M., and Csanaky, A., Experiences with L-deprenyl in Parkinsonism. J. neural Transm.43 (1978) 263–269.
Csanda, E., Tárczy, M., Takáts, A., Mogyrós, I., Köves, A., and Katona, G., L-Deprenyl in the treatment of Parkinson's disease. J. neural Transm., suppl. 19 (1983) 283–290.
Da Prada, M., and Zürcher, G., Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci.19 (1976) 1161–1174.
Da Prada, M., Bonetti, E.P., and Keller, H.H., Induction of mounting behavior in female and male rats after lisuride. Neurosci. Lett.6 (1977) 349–353.
Da Prada, M., Kettler, R., Keller, H.H., and Pieri, M., Einfluss von L-Deprenyl und Ergotderivaten auf das monoaminerge System der Ratte, in: Parkinson-Syndrom: Kombinations- und Begleit-Therapien, pp. 55–73., Ed. P.-A. Fisher. Schattauer Verlag, Stuttgart 1980.
Dreyfus, P.M., and Hauser, G., A simple micromethod for the collection of radioactive carbon dioxide in decarboxylation experiments. Mikrochim. Acta (1964) 150–151.
Duvoisin, R., Mendoza, M.R., Yahr, M.D., and Sweet, R.D., Bromocriptine as an adjuvant to levodopa, in: Dopamiergic ergot derivatives and motor function, pp. 329–335. Eds K. Fuxe and D.B. Calne. Wenner-Gren Center International Sympsoium vol. 31. Pergamon Press, Oxford 1979.
Ehinger, H., and Hornykiewicz, O., Verteilung von Noradrenalin und Dopamin im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des extrapyramidalen Systems. Klin. Wschr.38 (1960) 1236–1239.
Fahn, S., The ‘on-off’ phenomenon with levodopa therapy in parkinsonism: clinical and pharmacologic correlations and the effect of intramuscular pyridoxine. Neurology (Minneap.)24 (1974) 431–441.
Fahn, S., Cormi, R., Snider, S.R., and Prasad, A.L.N., Effect of a catechol-O-methyltransferase inhibitor, U-0521, with levodopa administrtion. Biochem. Pharmac.28 (1979) 1221–1225.
Fahn, S., Cote, L.J., Snider, S.R., Barrett, R.E., and Isgreen, W.P., Role of bromocriptine in the treatment of parkinsonism, in: Dopaminergic ergot derivatives and motor function, pp. 303–312. Eds K. Fuxe and D.B. Calne. Wenner-Gren Center International Symposium vol. 31. Pergamon Press, Oxford 1979.
Fuller, R.W., Clemens, J.A., Kornfeld, E.C., Snoddy, H.D., Smalstig, E.B., and Bach, N.J., Effect of (8β)-8-[(methylthio)methyl]-6-propylergoline on dopaminergic function and brain dopamine turnover in rats. Life Sci.24 (1979) 375–382.
Gauthier, G., de Auriaguerra, J., Simona, B., Constantinidis, J., Eisenring, J.J., Krassoïewitch, M., Yanniatis, G., and Tissot, R., Thérapeutique du syndrome parkinsonien par la L-Dopa associée à des inhibiteurs de la décarboxylase. Revue neurol.122 (1970) 297–319.
Glover, V., Sandler, M., Owen, F., and Riley, G.J., Dopamine is a monoamine oxidase B substrate in man. Nature265 (1977) 80–81.
Goetz, C.G., Tanner, C.M., Glantz, R., and Klawans, H.L., Pergolide in Parkinson's disease. Archs Neurol.40 (1983) 785–787.
Goldstein, M., Lieberman, A., Lew, J.Y., Asano, T., Rosenfeld, M.R, and Makman, M., Interaction of pergolide with central dopaminergic receptors. Proc. natl Acad. Sci. USA77 (1980) 3725–3728.
Gordonsmith, R.H., Raxworthy, M.J., and Gulliver, P.A., Substrate stereospecificity and selectivity of catechol-O-methyl-transferase for dopa, dopa derivatives and α-substituted catecholamines. Biochem. Pharmac.31 (1982) 433–437.
Gundert-Reny, U., Hildebradt, R., Stiehl, A., Weber, E., Zürcher, G., and Da Prada, M., Intestinal absorption of levodopa in man. Eur. J. Pharmac.25 (1983) 69–72.
Hornykiewicz, O., Biogenic amines in the central nervous system, in: Handbook of Clinical Neurology, vol. 29. Eds P.J., Vinken and G.W. Bruyn; Metabolic and Deficiency Diseases of the Nervous System, Pard III, pp. 459–483. Ed. H.L. Klawaus. North-Holland, Amsterdam 1977.
Hornykiewicz, O., Biochemical abnormalities in some extrastriatal neuronal systems in Parkinson's disease, in: Parkinson's disease —Current progress, problems and management, pp. 109–119. Eds U.K. Rinne, M. Klingler and G. Stamm. Elsevier/North-Holland, Amsterdam 1980.
Horowski, R., and Wachtel, H., Direct dopaminergic action of lisuride hydrogen maleate, an ergot derivative, in mice. Eur. J. Pharmac.36 (1976) 373–383.
Horowski, R., and Wachtel, H., Pharmacological effects of lisuride in rodents mediated by dopaminergic receptors: mechanism of action and influence of chronic treatment with lisuride, in: Dopaminergic ergot derivatives and motor function, pp. 237–249. Eds K. Fuxe and D.B. Calne. Wenner-Gren Center International Symposium, vol. 31. Pergamon Press, Oxrord 1979.
Johnson, G.A., Baker, C.A., and Smith, R.T., Radioenzymatic assay of sulfate conjugates of catecholamines and DOPA in plasma. Life Sci.26 (1980) 1591–1598.
Karoum, F., Chuang, L.-W., Eisler, T., Calne, D.B., Liebowitz, M.R., Quitkin, F.M., Klein, D.F., and Wyatt, R.J., Metabolism of (−)deprenyl to amphetamine and methamphetamine may be responsible for deprenyl's therapeutic benefit: A biochemical assessment. Neurology32 (1982) 503–509.
Kebabian, J. W., and Calne, D. B., Multiple receptors for dopamine. Naturology32 (1982) 503–509.
Kebabian, J. W., Kebabian, P. R., Munemura, M., and Calne, D. B. Dopaminergic ergots: drugs which discriminate between the multiple classes of dopamine receptors, in: Dopaminergic ergot derivatives and motor function, pp. 61–71. Eds K. Fuxe and D. B. Calne. Wenner-Gren Center International Symposium. Vol. 31. Pergamon Press, Oxford 1979.
Kehr, W., Effect of lisuride and other ergot derivatives on monoaminergic mechanisms in rat brain. Eur. J. Pharmac.41 (1977) 261–273.
Kehr, W., Neumeister, R., and Zimmerman, R., Action of ergot dopaminergic agonists on monoamine synthesis in rat brain, in: Dopaminergic ergot derivatives and motor function, pp. 173–186. Eds K. Fuxe and D. B. Calne. Wenner-Gren Center International Symposium, vol. 31. Pergamon Press, Oxford 1979.
Keller, H. H., Burkard, W. P., Pieri, L., Bonetti, E. P., and Da Prada, M., Lisuride- and LSD-induced changes of monoamine turnover in the rat brain. Adv. Biochem. Psychopharmac.19 (1978) 393–396.
Keller, H. H., Bonetti, E. P., Pieri, L., and Da Prada, M., Lisuride-induced mounting behavior and effects on the monoaminergic system in rat brain, in: Lisuride and other dopamine agonists, pp. 79–87. Eds B. D. Calne, R. Horowski, R. J. McDonald and W. Wuttke. Raven Press, New York 1983.
Knoll, J., and Magyar, K., Some puzzling pharmacological effects of monoamine oxidase inhibitors. Adv. Biochem. Pharmacol.5 (1972) 393–408.
Knoll, J., The pharmacology of selective irreversible monoamine oxidase inhibitors, in: Enzyme activated irrversible inhibitors, pp. 253–269. Eds N. Seiler, M. J. Jung and J. Koch-Weser. Elsevier-North Holland, Amsterdam 1978.
Knoll, J., (−)Deprenyl: the MAO inhibitor without the cheese effect. Trends Neurosci.2 (1979) 111–113.
Koller, W. C., Weiner, W. J., Diamond, B. I., Nansieda, P. A., and Klawans, H. L., The pharmacological evaluation of pergolide mesylate as a potential antiparkinson agent. Neuropharmacology19 (1980) 831–837.
Kostowski, W., Jerlicz, M., Bidzinski, A., and Hauptmann, M., Evidence for existence of two opposite noradrenergic brain systems controlling behavior. Psychopharmacologia, Berlin59 (1978) 311–312.
Kuruma, I., Bartholini, G., Tissot, R., and Pletscher, A., Comparative investigation of inhibitors of extracerebral dopa decarboxylase in man and rats. J. Pharm. Pharmac.24 (1972) 289–294.
Larsen, T. A., and Calne, D. B., Recent advances in the study of Parkinson's disease. Trends Neurosci.5 (1982) 10–12.
Lees, A. J., Kohout, L. J., Shaw, K. M., Stern, G. M., Elsworth, J. D., Sandler, M., and Youdim, M. B. H., Deprenyl in Parkinson's disease. Lancet2 (1977) 65–69.
Lees, A. J., and Stern, G. M., Sustained low-dose levodopa therapy in Parkinson's disease: a 3-year follow-up, in: Advances in Neurology Vol. 37, Experimental therapeutics of movement disorders, pp. 9–15. Eds S. Fahn, D. B. Calne and I. Shoulson. Raven Press, New York 1983.
Le Witt, P. A., and Calne, D. B., Recent advances in the treatment of Parkinson's disease: the role of bromocriptine. J. neural. Transm.51 (1981) 175–184.
Le Witt, P. A., Gopinatham, G., Ward, C. D., Sanes, J. N., Dambrosia, J. M., Durso, R., and Calne, D. B., Lisuride versus bromocriptine treatment in Parkinson disease: a double-blind study. Neurology32 (1982) 69–72.
Le Witt, P. A., Burns, R. S., and Calne, D. B., Lisuride treatment in Parkinson's disease: clinical and pharmacokinetic studies, in: Advances in Neurology Vol. 37, Experimental therapeutics of movement disorders, pp. 131–140. Eds S. Fahn, D. B. Calne and I. Shoulson. Raven Press, New York 1983.
Lieberman, A., Goodgold, A., and Jonas, S., Comparison of dopa decarboxylase inhibitor (carbidopa) combined with levodopa and levodopa alone in Parkinson's disease. Neurology (Minneap.)25 (1975) 911–916.
Lieberman, A., Kupersmith, M., Estey, E., and Goldstein, M., Treatment of Parkinson's disease with bromicriptine. N. Engl. J. Med.295 (1976) 1400–1404.
Lieberman, A., Goldstein, M., Leibowitz, M., Neophytides, A., Kupersmith, M., Pact, V., and Kleinberg, D., Treatment of advanced Parkinson disease with pergolide. Neurology31 (1981) 675–682.
Lieberman, A., Goldstein, M., Neophytides, A., Kupersmith, M., Leibowitz, M., Zasorin, N., Walker, R., and Kleinberg, D., Lisuride in Parkinson disease: efficacy of lisuride compared to levodopa. Neurology31 (1981) 961–965.
Lieberman, A., Neophytides, A., Leibowitz, M., Gopinathan, G., Pact, V., Walker, R., Goodgold, A., and Goldstein, M., Comparative efficacy of pergolide and bromocriptine in patients with advanced Parkinson's disease, in: Advances in Neurology vol. 37, Experimental therapeutics of movement disorders, pp. 95–108. Eds S. Fahn, D. B. Calne and I. Shoulson. Raven Press, New York 1983.
Markstein, R., Herrling, P. L., Bürki, H. R., Asper, H., and Ruch, W., The effect of bromocriptine on rat striatal adenylate cyclase and rat brain monoamine metabolism. J. Neurochem.31 (1978) 1163–1172.
Marsden, C. D., Parkes, J. D., and Rees, J. E., A comparison of treatment of Parkinson's disease with L-DOPA and with SinemetR, in: Current concepts in the treatment of Parkinsonism, pp. 21–35. Ed. M. D. Yahr. Raven Press, New York 1974.
Marsden, C. D., and Parkes, J. D., On-off' effects in patients with Parkinson's disease on chronic levodopa therapy. Lancet1 (1976) 292–296.
McLellan, D. L., and Dean, B. C., Improved control of brittle Parkinsonism by separate administration of levodopa and benserazide. Br. med. J.284 (1982) 1001–1002.
Narabayashi, H., Pharmacological basis of akinesia in Parkinson's disease. J. neural Transm., suppl. 19 (1983) 143–151.
Papavasiliou, P. S., Cotzias, G. C., and Duby, S. E., Levodopa in Parkinsonism: Potentiation of central effects with a peripheral inhibitor. N. Engl. J. Med.285 (1972) 8–14.
Parkes, J. D., Adverse effects of antiparkinsonian drugs. Drugs21 (1981) 341–353.
Parkes, J. D., Tarsy, D., Marsden, C. D., Bovill, K. T., Phipps, J. A., Rose, P., and Asselman, P., J. Neurol. Neurosurg. Psychiat.38 (1975) 232–237.
Pieri, L., Keller, H. H., Burkard, W. P., and Da Prada, M., Effects of lisuride and LSD on cerebral monoamine systems and hallucinosis. Nature272 (1978) 278–280.
Pieri, L., Keller, H. H., Laurent, J.-P., Burkard, W., Pieri, M., Bonetti, E. P., and Da Prada, M., Behavioural, neurochemical and electrophysiological effects of lisuride and LSD in animals, in: Lisuride and other dopamine agonists, pp. 89–96. Eds D. B. Calne, R. Horowski, R. J. McDonald and W. Wuttke. Raven Press, New York 1983.
Pieri, M., Pieri, L., Saner, A., Da Prada, M., and Haefely, W., A. comparison of drug-induced rotation in rats lesioned in the medial forebrain bundle with 5,6-dihydroxytryptamine or 6-hydroxydopamine. Archs int. Pharmacodyn. Ther.217 (1975) 118–130.
Pieri, M., Schaffner, R., Pieri, L., Da Prada, M., and Haefely, W., Turning in MFB-lesioned rats and antagonism of neuroleptic-induced catalepsy after lisuride and LSD. Life Sci.22 (1978) 1115–1121.
Pletscher, A., Effect of inhibitors of extracerebral decarboxylase on levodopa metabolism. Adv. Neurol.3 (1973) 49–58.
Rabey, J. M., Passettiner, P., Bystritsky, A., Engel, J., and Goldstein, M., The regulation of striatal DOPA synthesis by α2-adrenoceptors. Brain Res.230 (1981) 422–426.
Raches, A., and Fahn, S., O-Methyldopa interferes with striatal utilization of levodopa. Ann. Neurology10 (1981) 94–95.
Reynolds, G. P., Riederer, P., and Sandler, M., Amphetamine and 2-phenylethylamine in post-mortem parkinsonian brain after (−)deprenyl administration. J. neural Transm.43 (1978) 271–277.
Reynolds, G. P., Riederer, P., and Rausch, W.-D., Dopamine metabolism in human brain: effects of monoamine oxidase inhibition in vitro by (−)deprenyl and (+) and (−)tranylcypromine. J. neural Transm., suppl. 16 (1980) 173–178.
Riederer, P., Jelliger, K., Danlerczyk, W., Seemann, D., Ulm, G., Reynolds, G. P., Birkmayer, W., and Koppel, H., Combination treatment with selective monoamine oxidase inhibitors and dopaminergic agonists in Parkinson's disease: biochemical and clinical observations, in: Advances in Neurology Vol. 37, Experimental therapeutics of movement disorders, pp. 159–176. Eds S. Fahn, D. B. Calne and I. Shoulson. Raven Press, New York 1983.
Rinne, U. K., Siirtola, T., and Sonninen, V., L-Deprenyl treatment of on-off phenomena in Parkinson's disease. J. neural. Transm.43 (1978) 253–262.
Rinne, U. K., Martilla, R., and Sonninen, V., Relationship between brain dopamine turnover and therapeutic response to bromocriptine, in: Dopaminergic ergot derivatives and motor function, pp. 319–324, Eds K. Fuxe and D. B. Calne. Wenner-Gren Center International Symposium, vol. 31. Pergamon Press, Oxford 1979.
Rinne, U. K., and Mölsä, P., Levodopa with benserazide or carbidopa in Parkinson disease. Neurology29 (1979) 1584–1589.
Rinne, U. K., Klingler, M., and Stamm, G., eds, Parkinson's disease—Current progress, problems and management. Elsevier/North-Holland, Amsterdam 1980.
Rinne, U. K., Koskinen, V., and Lönnberg, P., Neurotransmitter receptors in the parkinsonian brain, in: Parkinson's disease—Current progress, problems and management, pp. 93–107. Eds U. K. Rinne, M. Klingler and G. Stamm. Elsevier/North-Holland, Amsterdam 1980.
Rinne, U. K., Treatment of Parkinson's disease: problems with a progressing disease. J. neural Transm.51 (1981) 161–174.
Rinne, U. K., Dopamine agonists in the treatment of Parkinson's disease, in: Advances in neurology Vol. 37, Experimental therapeutics of movement disorders, pp. 141–150. Eds S. Fahn, D. B. Calne and I. Shoulson. Raven Press, New York 1983.
Sandler, M., Glover, V., Ashford, A., and Stern, G. M., Absence of cheese-effect during deprenyl therapy: some recent studies. J. neural Transm.43 (1978) 209–215.
Scatton, B., Effect of dopamine agonists and neuroleptic agents on striatal acetylcholine transmission in the rat: evidence against dopamine receptor multiplicity. J. Pharmac. exp. Ther.220 (1982) 197–220.
Schachter, M., Bedard, P., Debono, A. G., Jenner, P., Marsden, C. D., Price, P., Parkes, J. D., Keeman, J., Smith, B., Rosenthaler, J. J., Horowski, R., and Dorow, R., The role of D1 and D2 receptors. Nature, Lond.286 (1980) 157–159.
Seeman, P., Brain dopamine receptors. Pharmac. Rev.32 (1980) 230–287.
Sethy, V. H., Regulation of striatal acetylcholine concentration by D2-dopamine receptors. Eur. J. Pharmac.60 (1979) 397–398.
Siegfried, J., Klaiber, R., Perret, E., and Ziegler, W. H., Behandlung des Morbus Parkinson mit L-Dopa in Kombination mit einem Decarboxylaschemmer. Dt. med. Wschr.94 (1969) 2678.
Silbergeld, E. K., Hruska, R. E., Weir, R., and Kennedy, S. W., Dopaminergic and serotoninergic effects of ergot drugs, in: Dopaminergic ergot derivatives and motor function, pp. 223–235. Eds K. Fuxe and D. B. Calne. Wenner-Gren Center International Symposium, vol. 31. Pergamon Press, Oxford 1979.
Simpson, L. L., Evidence that deprenyl, a type B monoamine oxidase inhibitor, is an indirectly acting sympathomimetic amine. Biochem. Pharmac.27 (1978) 1591–1595.
Thorner, M. D., Flückiger, E., and Calne, D. B., Bromocriptine—A clinical and pharmacological review. Raven Press, New York 1980.
Tissot, R., Eisenring, J.-J., and Constantinidis, J., Modes of action and optimal dosage of decarboxylase inhibitors, in: Current concepts in the treatment of Parkinsonism, pp. 123–132. Ed. M. D. Yahr. Raven Press, New York 1974.
Ungerstedt, U., and Arbuthnott, G. W., Quantitative recording of rotational behavior in rats after 6-OH-dopamine lesions of the nigrostriatal system. Brain Res.24 (1970) 485–493.
Ungerstedt, U., Avemo, A., Avemo, E., Ljungberg, T., and Ranje, C., Animal models of Parkinsonism, in: Advances in Neurology, vol. 3, pp. 257–271. Ed. D. B. Calne. Raven Press, New York 1973.
Yahr, M. D., Duvoisin, R. C., and Mendoza, M. R., Modification of L-Dopa therapy of parkinsonism by alpha-methyldopa hydrazine (MK-486). Trans. Am. neurol. Assoc.96 (1971) 55–58.
Yahr, M. D., Overview of present day treatment of Parkinson's disease. J. neural Transm.43 (1978) 227–238.
Zürcher, G., and Da Prada, M., Radioenzymatic assay of femtomole concentrations of DOPA in tissues and body fluids. J. Neurochem.33 (1979) 631–639.
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Da Prada, M., Keller, H.H., Pieri, L. et al. The pharmacology of Parkinson's disease: Basic aspects and recent advances. Experientia 40, 1165–1172 (1984). https://doi.org/10.1007/BF01946641
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DOI: https://doi.org/10.1007/BF01946641