The purpose of this two-part review is to explain current drug treatment in part I and discuss investigational drug therapy and miscellaneous drugs in the management of parkinsonism in part II. The medical approach to this disease is still based on the imbalance between a deficiency of dopamine and a functional increase in acetylcholine. Anticholinergic agents are used to treat the tremors in the early stages of the disease.
KatzmanR. Degenerative and heterodegenerative diseases. In: MerrittH, ed. A textbook of neurology. Philadelphia: Lea and Febiger; 1979: 509–29.
2.
HoehnMMYahrMD. Parkinsonism: onset, progression, and mortality. Neurology1967; 17: 427–42.
3.
MarttilaRJRinneUKHalonenPMaddenDLSeverJL. Herpes viruses and parkinsonism: herpes simplex virus types 1 and 2, and cytomegalovirus antibodies in serum and CSF. Arch Neurol1981; 38: 19–21.
4.
LiebermanA. Parkinson's disease: a clinical review. Am J Med Sci1974; 267: 66–80.
5.
CanterGDe La TorreRMierM. A method for evaluating disability in patients with Parkinson's disease. J Nerv Ment Dis1961; 33: 143–7.
6.
DiamondSMarkhamC. Evaluating the evaluations: or how to weigh the scales of parkinsonian disability. Neurology1983; 33: 1098–9.
7.
WilliamsGR. Morbidity and mortality with parkinsonism. J Neurosurg1966; 24: 138–43.
8.
CarpenterMB. Anatomical organization of the corpus striatim and related nuclei. In: YahrM, ed. The basal ganglia. New York: Raven Press; 1976: 1–36.
9.
AndenNEFuxeKHambergerBHokfeltT. A quantitative study on the nigro-neostriatal dopamine neuron system in the rat. Acta Physiol Scand1966; 67: 306–12.
10.
HornykiewiczO. Neurohumoral interactions and basal ganglia function and dysfunction. In: YahrM, ed. The basal ganglia. New York: Raven Press; 1976: 269–80.
11.
KlawansHL. The pharmacology of tardive dyskinesias. Am J Psychiatry1976; 130: 82–6.
12.
CoolsARVan RossumJM. Excitation-mediating and inhibition-mediating dopamine receptors: a new concept towards a better understanding of electrophysiological, biochemical, pharmacological function and clinical data. Psychopharmacologia1976; 45: 243–54.
13.
KebabianJWCalneDB. Multiple receptors for dopamine. Nature1976; 277: 93–6.
14.
CalneDBKebabianJWSilbergeldEEvartsA. Advances in the neuropharmacology of parkinsonism. Ann Intern Med1979; 90: 219–29.
15.
KebabianJW. Dopamine-sensitive adenylyl cyclase: a receptor mechanism for dopamine. Adv Biochem Psychopharmacol1978; 19: 131–54.
16.
McLennaHYorkDA. The action of dopamine on neurons of the caudate nucleus. J Physiol1967; 189: 393–402.
17.
UngerstU. Postsynaptic supersensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand1971; 376 (suppl): 69–73.
18.
AghahajanianGKBunneyBS. Dopamine “autoreceptors”: pharmacological characerization by microiontophoretic single cell recording studies. NS Arch Pharmacol1977; 297: 1–7.
19.
KehrWCarlssonALindquistMMagnussonTAtackC. Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylast activity (letter). J Pharm Pharmacol1972; 24: 744–6.
20.
CarlssonA. Receptor-mediated control of dopamine metabolism. In: UdsinEBunneyWE, eds. Pre and post synaptic receptors. New York: Marcel Dekker; 1975: 49–65.
21.
TrabucchiMSpanoPFFrattolaL. Effects of bromocriptine on central dopaminergic receptors. Life Sci1976; 19: 225–32.
22.
KebabianJWCalneDBKebabianPR. Lergotrile mesylate: an in vivo dopamine agonist which blocks dopamine receptors in vitro. Commun Psychopharmacol1977; 1: 311–8.
23.
CohenMMSchiefeRT. Pharmacotherapy of Parkinson's disease. Am J Hosp Pharm1977; 34: 531–8.
24.
HalletM. Drug therapy of Parkinson's disease: rational therapy depends on selecting the appropriate drug. Hosp Formul Manage1979; 14: 85–7.
25.
HurigHI. Anticholinergics for Parkinson disease (letter). Ann Neurol1980; 170: 495.
26.
CotziasGCPapavasiliouPSGirosJZ. Therapeutic approaches in Parkinson's disease: possible roles of growth hormone and somatostatin. In: YahrM, ed. The basal ganglia. New York: Raven Press; 1976: 305–15.
27.
LevineJ, ed. Drug topics: annual pharmacists reference (red book). Oradell, NJ: Medical Economics Company, April 1985.
28.
SinghMMSmithJM. Reversal of some therapeutic effects of antipsychotic agents by an antiparkinsonism drug. J Nerv Ment Dis1973; 157: 50–8.
29.
HanstenPD. Drug interactions. 4th ed.Philadelphia: Lea and Febiger, 1979: 271.
30.
FermaglichJO'DohertyDS. Effect of gastric motility on L-dopa. Dis Nerv Syst1972; 33: 624–5.
31.
AlgeriSCerlettiCCurcioMEffects of anticholinergic drugs on gastrointestinal absorption of L-dopa in rats and man. Eur J Pharmacol1976; 35: 293–9.
32.
PostlethwaiteAERamsdellCMKelleyWN. Uricosuric effect of an anticholinergic agent in hyperuricemic subjects. Arch Intern Med1974; 134: 270–5.
33.
SalterRH. Hazards of sudden drug withdrawal. Practitioner1977; 218: 871–3.
34.
RileyTLMasseyEW. Managing the patient with Parkinson's disease. Postgrad Med1980; 66: 85–92.
35.
McDowellFH. The choice of drugs for Parkinson's disease. In: ModellW, ed. Drugs of choice 1980–1981. St. Louis: CV Mosby, 1980: 290–4.
36.
WeintraubMIVan WoertMH. Reversal by L-dopa of cholinergic hypersensitivity in Parkinson's disease. N Engl J Med1971; 284: 412–5.
37.
SasaharaKNitanaiTHabaraTMoriokaTNakajimaE. Dosage form design for improvement of bioavailability of L-dopa II: bioavailability of marketed L-dopa preparations in dogs and parkinsonian patients. J Pharm Sci1980; 69: 261–5.
38.
SasaharaKNitanaiTHabaraTMoriokaTNakajimaE. Dosage form design for improvement of bioavailability of L-dopa III: influence of dose on pharmacokinetic behavior of L-dopa in dogs and parkinsonian patients. J Pharm Sci1980; 69: 1374–8.
39.
BlanchineJRShawGM. Clinical pharmacokinetics of L-dopa in Parkinson's disease. Clin Pharmacokinet1976; 1: 312–38.
40.
MenaICotziasGC. Protein intake and treatment of Parkinson's disease with L-dopa. N Engl J Med1975; 292: 181–4.
41.
FinchamRWDeckerDA. L-dopa therapy in Parkinson's disease (a year's experience with 20 patients). J Iowa Med Soc1970; 60: 755–9.
42.
Levodopa carbidopa 92:00. In: McEvoyGK, ed. American Hospital Formulary Service Drug Information 86. Bethesda, MD: American Society of Hospital Pharmacists, 1986: 1912–7.
43.
KlawansHL. What to do when Sinemet fails: part one. Clin Neuropharmacol1984; 7: 121–33.
44.
KoellaWPSutinJ. Extra-blood-brain barrier brain structures. Int Rev Neurobiol1967; 10: 31–55.
45.
GoldbergCLWhitsettTL. Cardiovascular effects of L-dopa. JAMA1976; 218: 1921–3.
46.
SkibbaJLPinckleyJGilbertEFJohnsonRO. Multiple primary melanoma following administration of L-dopa. Arch Pathol1972; 93: 556–61.
47.
RobinsonEWajsbortJMekoriT. Effect of L-dopa on transplanted malignant melanomas in mice. Isr J Med Sci1973; 9: 1062–3.
48.
LiebermanANShupackJL. L-dopa and melanoma. Neurology1974; 24: 340–2.
49.
SweetRDMcDowellRHFeigensonJSLorangerHWGoodellH. Mental symptoms in Parkinson's disease during chronic treatment with L-dopa. Neurology1976; 26: 305–10.
50.
SweetRDMcDowellRH. Five years' treatment of Parkinson's disease with L-dopa. Ann Intern Med1975; 83: 456–63.
51.
GoodwinFK. Psychiatric side effects of L-dopa in man. JAMA1976; 218: 1915–20.
52.
LangrallHMJosephC. Evaluation of safety and efficacy of L-dopa in Parkinson's disease and syndrome. Neurology1972; 22 (suppl): 3–14.
53.
FahnSSniderSRPrasadALN. Normalization of brain serotonin in L-dopa-treated rats by L-tryptophan (abstract). Neurology1975; 25: 377.
54.
ChaseTNHoldenEMBrodyJA. L-dopa-induced dyskinesias comparison in parkinsonism-dementia and amyotrophic lateral sclerosis. Arch Neurol1973; 29: 328–30.
55.
RosenbergPHerishanuYBeilinB. Increased appetite (bulimia) in Parkinson's disease. J Am Geriatr Soc1977; 25: 277–8.
56.
DuvoisinRC. Pyridoxine as an adjunct in the treatment of parkinsonism. In: YahrM, ed. Advances in neurology. Vol. 2. New York: Raven Press; 1973: 229–48.
MorganJP. Isoniazide and L-dopa (letter). Ann Intern Med1980; 92: 434.
59.
LeonASSpiegelHEThomasGAbramsWB. Pyridoxine antagonism of L-dopa in parkinsonism. JAMA1971; 218: 1924–7.
60.
KlawansHLRingelSPShenkerDM. Failure of vitamin B6 to reverse the L-dopa effect in patients on a dopa decarboxylase inhibitor. J Neurol Neurosurg Psychiatry1971; 34: 682–6.
61.
BarbeauA. Six years of high-level L-dopa therapy in severely akinetic parkinsonian patients. Arch Neurol1976; 33: 333–8.
62.
BattistinLMeneghettiGRigottiSSaiaA. Long-term treatment of Parkinson's disease with L-dopa and dopadecarboxylase inhibitor: therapeutic results and side effects. Acta Neurol Scand1978; 57: 186–92.
63.
DelaneyPFermaglichJ. Parkinsonism and L-dopa: a five-year experience. J Clin Pharmacol1976; 16: 652–9.
64.
DiamondSGMarkhamCHH. Present mortality in Parkinson's disease: the ratio of observed to expected deaths with a method to calculate expected deaths. J Neurol Trans1976; 38: 259–69.
65.
JosephCChassanJBKochML. L-dopa in Parkinson's disease: a long-term appraisal of mortality. Ann Neurol1978; 3: 116–8.
66.
MarsdenCDParkesJD. Success and problems of long-term L-dopa therapy in Parkinson's disease. Lancet1977; 1: 345–9.
67.
MuenterMDSharplessNS. tyce gm, darley fl. Patterns of dystonia (“I-D-I” and “D-I-D”) in response to l-dopa therapy for Parkinson's disease. Mayo Clin Proc1977; 52: 163–74.
68.
BirdsongJHMcKinneyAS. Long-range motor performance changes in L-dopa-treated patients with Parkinson's disease. Neurology1974; 24: 107–15.
69.
ReisineTDFieldsJZYamamuraHI. Neurotransmitter receptor alterations in Parkinson's disease. Life Sci1977; 21: 335–44.
70.
LeserRPFahnSSniderSRCoteLJIsgreenWPBarrettRE. Analysis of the clinical problems in parkinsonism and the complications of long-term L-dopa therapy. Neurology1979; 29: 1253–60.
71.
LeeTSeemanPRajputAFarleyLJHornykiewiczO. Receptor basis for dopaminergic supersensitivity in Parkinson's disease. Nature1978; 273: 59–61.
72.
FahnSCalneDB. Considerations in the management of parkinsonism. Neurology1978; 28: 5–7.
73.
HoehnMM. Increased dosage of carbidopa in patients with Parkinson's disease receiving low doses of L-dopa: a pilot study. Arch Neurol1980; 37: 146–9.
74.
JaffeME. Clinical studies of carbidopa and l-dopa in the treatment of Parkinson's disease. In: YahrM, ed. Advances in neurology. Vol. 2. New York: Raven Press; 1973: 161–72.
75.
TourtellotteWWSyndulkoKPotvinARHirschSBPotvinJH. Increased ratio of carbidopa to levodopa in treatment of Parkinson's disease. Arch Neurol1980; 37: 723–6.
76.
Carbidopa available as single agent. FDA Drug Bull1979; 9: 29.
77.
BianchineJR. Drugs for Parkinson's disease: centrally acting muscle relaxants. In: GoodmanLSGilmanA, eds. Goodman and Gilman's the pharmacological basis of therapeutics. 7th ed.New York: Macmillan; 1985: 473–90.
78.
WingertTDHershmanJM. Sinemet and thyroid function in Parkinson's disease. Neurology1979; 29: 1073–4.
79.
MarsH. Effect of pyridoxine or systemic l-dopa metabolism. In: YahrM, ed. Advances in neurology. Vol. 2. New York: Raven Press; 1973: 249–54.
80.
HunterKRSternGMLaurenceDR. Amantadine in parkinsonism. Lancet1970; 1: 1127–9.
81.
SchwabRSEnglandACPoskanzerDCYoungRR. Amantadine in the treatment of Parkinson's disease. JAMA1969; 208: 1168–70.
82.
StrömbergUSvenssonTHWaldecKB. On the mode of action of amantadine. J Pharm Pharmacol1970; 22: 959–61.
83.
TinberlakeWHVanceMA. Four-year treatment of patients with parkinsonism using amantadine alone or with L-dopa. Ann Neurol1978; 3: 119–28.
84.
SchwabRSPoskanzerDCEnglandACYoungRR. Amantadine in Parkinson's disease: review of more than two years experience. JAMA1972; 222: 792–5.
85.
ButzerJFSilverDESahsAL. Amantadine in Parkinson's disease: a double-blind, placebo-controlled, crossover study with long-term follow-up. Neurology1975; 25: 603–6.
86.
ShealyCNWeethJBMercierD. Livedo reticularis in patients with parkinsonism receiving amantadine. JAMA1970; 212: 1522–3.
87.
FahnSIsgreenWP. Long-term evaluation of amantadine and L-dopa combination in parkinsonism by double-blind crossover analysis. Neurology1975; 25: 695–700.
88.
KellerHHDapradaM. Central dopamine agonistic activity and microsomal biotransformation of lisuride, lergotrile and bromocriptine. Life Sci1979; 24: 1211–22.
89.
CotziasGCLawrenceWHPapavasiliouPSDubySEGinosJZMenaL. Apomorphine and parkinsonism. Trans Am Neurol Assoc1972; 97: 156–8.
90.
CotziasGCPapavasiliouPSTolosaESMendezJSBellmiduraM. Treatment of Parkinson's disease with aporphines. N Engl J Med1976; 294: 567–72.
91.
PapavasiliouPSCotziasGCRosalVLFMillerST. Treatment of parkinsonism with N-n-propyl norapomorphine and L-dopa (with or without carbidopa). Arch Neurol1978; 35: 787–91.
92.
SilbergeldEKPfeifferRF. Differential effects of three dopamine agonists: apomorphine, bromocriptine and lergotrile. J Neurochem1977; 28: 1323–6.
93.
ParkesJD. Bromocriptine in the treatment of parkinsonism. Drugs1979; 17: 365–82.
TrabucchiMSpanoPFTononGCFrattolaL. Effects of bromocriptine on central dopaminergic receptors. Life Sci1976; 19: 225–32.
96.
SchwarczRFuxeKAgnatiLFGustafssonJA. Effects of bromocriptine on 3H-spiroperidol binding sites in rat striatum. Evidence for actions of dopamine receptors not linked to adelnylate cyclase. Life Sci1978; 23: 465–70.
97.
LewJYHataFOhashiTGoldsteinM. The interactions of bromocriptine and lergotrile with dopamine and α-adrenergic receptors. J Neural Transm1977; 41: 109–21.
98.
HoroskiR. Differences in the dopaminergic effects of the ergot derivatives bromocriptine, lisuride, and D-LSD as compared with apomorphine. Eur J Pharmacol1978; 51: 157–66.
99.
HuttCSSinderSRFahnS. Interaction between bromocriptine and L-dopa. Biochemical basis for an improved treatment for parkinsonism. Neurology1977; 27: 505–10.
100.
VanloonGRSoleMJRuseJL. Effects of bromocriptine on plasma catecholamines in normal men. Neuroendocrinology1978; 28: 425–34.
101.
MajJGancarcyzkLRowlowA. The influence of bromocriptine on serotonin neurons. J Neural Transm1977; 41: 253–64.
CalneDBWilliamsACNuttJGNeophytidesAEislerTTeychennePF. Ergot derivatives for parkinsonism. Med J Aust1978; 2: 25–6.
104.
FriisMLGronULarsenNEPakkenbergHHuidbergEF. Pharmacokinetics of bromocriptine during continuous oral treatment of Parkinson's disease. Eur J Clin Pharmacol1979; 15: 275–80.
105.
TeychennePFPfeifferRFBernSMMcInturffDCalneDB. Comparison between lergotrile and bromocriptine in parkinsonism. Ann Neurol1978; 3: 319–24.
106.
FahnSCoteLJSniderSRBarrettREIsgreenWP. The role of bromocriptine in the treatment of parkinsonism. Neurology1979; 29: 1077–83.
107.
FahnSCoteLJSniderSRBarrettREIsgreenWP. Efficacy and toxicity of bromocriptine in the treatment of parkinsonism (abstract). Neurology1978; 28: 343.
108.
LiebermanANKupersmithMGopinathanGEsteyEGoodgoldAGoldsteinM. Further studies with bromocriptine in Parkinson's disease (abstract). Neurology1978; 28: 343.
109.
TeychennePFRosinAJPlotkinCNCalneDB. Crosstolerance between two dopaminergic ergot derivatives bromocriptine and lergotrile. Br J Clin Pharmacol1980; 9: 47–50.
110.
LiebermanAKupersmithMNeophytidesALong-term efficacy of bromocriptine in Parkinson's disease. Neurology1980; 30: 518–23.
111.
FahnS. “On-off” phenomenon with L-dopa therapy in parkinsonism. Neurology1974; 24: 431–41.
112.
MarsdenCDParkesJD. “On-Off” effects in patients with Parkinson's disease on chronic L-dopa therapy. Lancet1976; 1: 292–6.
113.
KlawansHTannerCGlattSGoetzCG. A 6-month trial of pergolide mesylate in the treatment of Parkinson's disease. Adv Neurol1983; 37: 75–83.
114.
BarbeauA. Long-term appraisal of L-dopa therapy. Neurology1972; 22 (suppl): 22–4.
115.
WeinerWJKollerWCPerlikSNausiedaPAKlawansHL. Drug holiday and management of Parkinson's disease. Neurology1980; 30: 1257–61.
116.
RosinAJDevereuxDEngNCalneDB. Parkinsonism with “on-off” phenomena intravenous treatment with L-dopa after major abdominal surgery. Arch Neurol1979; 35: 32–4.
117.
KollerWCWeinerWJPerlikSNausiedaPAKlawansHL. Long-term efficacy of drug holiday in the management of the complications of chronic L-dopa therapy in parkinsonism (abstract). Neurology1980; 30: 365.
118.
GoetzCGTannerCMNausiedaPA. Weekly drug holiday in Parkinson's disease. Neurology1981; 31: 1460–2.
119.
DirenfeldKLFeldmanRGAlexanderMPKelly-HayesM. Is levodopa drug holiday useful?Neurology1980; 30: 785–8.
120.
FeigensonJSSweetRDMcDowellFH. Piribedil: its synergistic effect in multi-drug regimens for parkinsonism. Neurology1976; 26: 430–3.
121.
NuttJGWoodwardWRHammerstadJPCarterJHAndersonJL. The “on-off” phenomenon in Parkinson's disease. N Engl J Med1984; 310: 483–8.