Beans, roots and leaves A History of the Chemical Therapy of Parkinsonism

876 Pages·2001·9.33 MB·English

by  Paul Foley

Beans, roots and leaves

A History of the Chemical Therapy
of Parkinsonism

by

Paul Bernard Foley
B.Sc. (Hons) (Macquarie), M.A. (Würzburg)

Doctoral dissertation submitted to the Bavarian Julius Maximilian University,

Würzburg (2001)

Irrtum verläßt uns nie,
doch zieht ein höheres Bedürfnis
immer den strebenden Geist

leise zur Wahrheit hinan.

Johann Wolfgang von Goethe
(Vier Jahreszeiten: Sommer)

Eingereicht am: 15. Juni 2001.............................................................................................

Mitglieder der Promotionskommission:

Vorsitzender: Professor Dr. Werner Goebel (Dekan).........................................................

Gutachter: Professor Dr. Dr. Gundolf Keil..........................................................................

Gutachter: Professor Dr. Erich Buchner..............................................................................

Tag des Promotionskolloquiums: 12. Juli 2001..................................................................

Doktorurkunde ausgehändigt: .............................................................................................

Table of contents

Table of figures XV
Table of tables XIX
Table of boxes XVII
Acknowledgements XIX
Foreword XXV
Explanatory notes XXVII

I. PARKINSONISM BEFORE PARKINSON 1
Defining “parkinsonism” 12
India: parkinsonism and Mucuna pruriens 15
Other traditional antiparkinsonian therapies 23
Vicia faba 25

PART I: THE ALKALOID THERAPIES
II. THERAPY OF PARKINSONISM IN THE FIRST HALF OF THE NINETEENTH
CENTURY 31
Therapy for parkinsonism from the middle of the 19th century 36

III. THE SOLANACEOUS ALKALOIDS 41
John Harley and The Old Vegetable Neurotics 47
Alkaloids from the solanaceous plants 50
Belladonna (Atropa belladonna Linnaeus), atropine and hyoscyamine 53
Henbane or Hyoscyamus (Hyoscyamus niger Linnaeus) 59
Duboisia (Australian corkwood; Duboisia myoporoides Robert Brown) 63
VII
Table of contents
Hyoscine: the “second alkaloid” of hyoscyamus 68
Scopolamine 71

IV. ALKALOIDS IN THE THERAPY OF PARKINSONISM: FROM CHARCOT TO
THE OUTBREAK OF ENCEPHALITIS EPIDEMICA 77
Duboisine 81
Wilhelm Erb and hyoscine 83
Hyoscyamine or hyoscine therapy? 88
Other agents employed in the therapy of parkinsonism in the 19th century 90
Hypotheses regarding the cause of parkinsonism at the turn of the century 96
Pharmacological therapy at the beginning of the 20th century 100
Organotherapy 104

V. ENCEPHALITIS LETHARGICA: NEW STRATEGIES IN THE THERAPY OF
PARKINSONISM 109
The etiology of parkinsonism: neuropathology of the extrapyramidal system 113
Neurosurgical approaches to parkinsonism 119
The initial responses to post-encephalitic parkinsonism: attempts to address the viral
disorder 122
Treatment with induced fever 124
Radiation therapy: X-ray and ultraviolet therapy 126
Serum therapies 128
Miscellaneous therapies directed against the presumed viral basis 129
Pharmacological intervention in post-encephalitic parkinsonism: symptomatic treatment 133
Psychological factors and antiparkinsonian therapy 135
Hyoscine/Scopolamine 137
Gelsemium 145
Stramonium 145
VIII
Table of contents
Bulbocapnine 152
Nicotine and curare 157
Striaphorin and Neurosmon 161
The harmala alkaloids 164

VI. THE 1930 AND 1940 : THE DOMINANCE OF ATROPINE AND
S S
BELLADONNA 183
High dose atropine: the “Römer” or “Hirsau therapy” 185
Combination therapies 197
The Bulgarian treatment 198
Response to the Bulgarian therapy 206
Mechanism of action of the Bulgarian therapy 208
Side effects and contraindications 214
The Bulgarian treatment in Germany 216
The Bulgarian treatment in England 222
The Bulgarian treatment in America 226
The Bulgarian treatment: concluding remarks 230
Belladonnine and apoatropine 231
Other alkaloids of the belladonna root 237
Mood altering drugs in the treatment of parkinsonism: stimulants and sedatives 238
Miscellaneous therapy attempts 241
The situation in 1945 244

PART II: THE SYNTHETIC ANTIPARKINSONIAN PREPARATIONS
VII. THE 1950 : THE SYNTHETIC ANTICHOLINERGIC AND
S
ANTIHISTAMINERGIC PREPARATIONS 251
Introductory remarks: Theoretical considerations at the commencement of the 1950s 252
The introduction of synthetic drugs for parkinsonism 257
IX
Table of contents
Phenothiazine derivatives 263
Benzhexol HCl (‘Artane’) and congeners 270
Benztropine mesylate (‘Cogentin’) and congeners 278
Antihistaminergic agents 280
Miscellaneous synthetic anticholinergic agents 287
Tigloidine (Tiglyl-ψ-tropine) 291
Sympathomimetic agents 292
Apomorphine 294
Energizers and sedatives 298
Pyridoxine (Vitamin B ) 303
6
Miscellaneous agents 307
Problems associated with the anticholinergic therapy of parkinsonism 309
Outlook for antiparkinsonian therapy at the beginning of the 1960s 313

VIII. ASSESSMENT OF THE PHARMACOLOGICAL THERAPY OF
PARKINSONISM 317
Which were the “drugs of choice”? 318
Comparing different antiparkinsonian agents 322
Problems in the assessment of antiparkinsonian medication 326
Objective measures in the assessment of antiparkinsonian agents 332
Target symptoms in the therapy of parkinsonism 336
Other problems in the comparison of antiparkinsonian medications 338
Outlook for antiparkinsonian therapy at the beginning of the 1960s 342

IX. WHY WAS THE ANTICHOLINERGIC THERAPY OF PARKINSONISM
SUCCESSFUL? 349
Evidence for the involvement of cholinergic systems in parkinsonism 352
Animal models for the testing of antiparkinsonian agents 353
X