[imark3000]

Any one using anticholinergics which was once used as only medicine for PD?
http://www.ask.com/bar?q=anticholine...holinergic.htm


Parkinson’s disease (paralysis agitans) is a neurological disorder which principally strikes individuals of middle age and older. In the general population, Parkinson's disease affects approximately 1 in 1000 people (1). It has been estimated that in persons aged 65 years and older, the incidence is approximately 1% (2). From a biochemical perspective, Parkinson's is thought to be caused by degeneration of dopaminergic neurons in the neostriatum, a region of the basal ganglia in the brain important in the regulation of neural impulses which control motor functions (3-5). Although the primary agents used for the pharmacological treatment of Parkinson’s disease are those which directly or indirectly act as dopamine agonists, the first drugs used in its treatment were those with anticholinergic activity (4). It was not until the late 1960’s that the use of levodopa (L-dopa) for the treatment of Parkinson’s disease was established. Although L-dopa has proved to be a monumental advance in the treatment of Parkinson’s disease, by itself it is not curative nor sufficient to completely alleviate the symptoms of the disease, which typically include an involuntary resting tremor, muscular weakness, bradykinesia, and muscular rigidity (5). Further, the usefulness of dopamine is limited by a “wearing-off” phenomenon which appears with prolonged usage (3-5). Although much attention has been directed by researchers and the pharmaceutical industry towards the understanding and development of pharmacological agents which modulate dopaminergic pathways, relatively little effort has been placed towards understanding the pharmacokinetics of those drugs which act at the level of the cholinergic system (1).

The anticholinergic drugs used in the treatment of Parkinson's disease (ACP), despite their adjunct role, are nevertheless important agents as they provide an alternate mechanism of action which may alleviate some of the troublesome symptoms of the disease, in particular the involuntary resting tremor. They are used as monotherapy early in the course of the disease, and act synergistically with L-dopa in more advanced stages (3-5). Because ACP are used early in the disease progression, they are potentially helpful in delaying the need for L-dopa treatment. This may allow the patient to derive optimal use of L-dopa later in the course of the disease. In addition, they may allow for a reduction in the dose of L-dopa required in more advanced cases, thus further extending the use of L-dopa (6). The ACP are clinically useful in another respect, as they can diminish the extrapyramidal side effects associated with the use of antipsychotic agents.The purpose of this article is to outline similarities and differences between the ACP, and to highlight deficiencies in the current state of pharmacokinetic knowledge.

Mechanism of action of anticholinergics used in

[lurkingforacure]

I posted about this before but just a reminder, there are articles out there that link cognitive changes with anticholinergics. When the drug is stopped, the dementia/memory problems go away (this is not to say that if you have dementia already, it will be negated if you start taking these drugs and then stop them) so do the research before taking these.

[paula_w]

I took this drug in the beginning before l-dopa. it really helped the rigidity, but i was not in the real world; it was like an invisible wall was there between me and the world and I was still teaching.

However, now that i see it is being used for advanced; i must say that i do recall relief and relaxing of my symptoms and i may inquire at my neuro's about its' use now. i didn't want to give it up - had to.

paula

[reverett123]

A fascinating and massive (800+ pgs) doctoral thesis (and now a book) entitled "Beans, Roots, and Leaves" by (now Dr.) Paul Bernard Foley can be found for free as his thesis or purchased from Amazon as his book. Every PWP should have it. The table of contents hints at what a masterwork it is:

1
I. PARKINSONISM BEFORE PARKINSON
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 1930S AND 1940S: THE DOMINANCE OF ATROPINE AND
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 1950S: THE SYNTHETIC ANTICHOLINERGIC AND
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- -tropine)
291
Sympathomimetic agents
292
Apomorphine
294
Energizers and sedatives
298
303
Pyridoxine (Vitamin B6)
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

Table of contents

Lesion models of parkinsonism
357
Tremorine
359
New directions in understanding anticholinergic therapy
363
Problems concerning the development of a model for the testing of antiparkinsonian drugs

365
The pharmacokinetics of the anticholinergic antiparkinsonian drugs 374
Summation: why were the anticholinergic antiparkinsonian agents successful? 375

PART III: DOPAMINE
379
X. THE DOPAMINE AND L-DOPA STORY
380
Dopamine and L-DOPA: the beginnings
L-DOPA and dopamine as precursors of adrenaline: Holtz and DOPA decarboxylase 386
The localization of brain catecholamines
392
Dopamine as precursor of adrenaline: Blaschko
395
Reserpine and chlorpromazine: drug-induced human models of parkinsonism 398
The biochemical effects of reserpine
406
410
Carlsson, reserpine and L-DOPA
Identification of dopamine in the brain
413
The First International Symposium on Catecholamines at the National Institutes for Health,
Bethesda, October 16-18, 1958
419
Isamu Sano and the first Japanese contribution to the L-DOPA story 423
426
Metabolism of L-DOPA/dopamine in the brain
The Ciba Foundation Symposium on Adrenergic Mechanisms, 28-31 March 1960, London 426
The Bel-Air Symposium on Monoamines and the Central Nervous System,
September 1961
435

XI. THE FIRST L-DOPA TRIALS IN THE CLINIC: FRANKFURT AND OSAKA 441
Frankfurt: demonstration of the anti-reserpine effects of L-DOPA in man 442
453
Isamu Sano and the first Japanese L-DOPA trial
XI

Table of contents

XII. VIENNA TALES: DISCOVERY OF THE DOPAMINE DEFICIT AND
459
INTRODUCTION OF L-DOPA THERAPY
Walther Birkmayer: Background
460
Oleh Hornykiewicz: the background
462
Birkmayer, Hornykiewicz and Parkinson’s disease
463
The controversy regarding credit for the L-DOPA experiment in Vienna 472
474
Further exploration of the “L-DOPA effect”
477
Dopamine and L-DOPA in other laboratories
Pharmacology of the L-DOPA effect: Hornykiewicz and Bernheimer 479
490
Further investigation of L-DOPA in the clinic: Birkmayer

XIII. MONTRÉAL AND GÖTEBORG: THE DOPAMINE DEFICIT, L-DOPA
THERAPY AND THE NIGROSTRIATAL PATHWAY
495
506
L-DOPA therapy in Montréal
The rediscovery of the nigrostriatal pathway
513
Visualization of the nigrostriatal pathway
518

525
XIV. THE “LEAN YEARS”: L-DOPA THERAPY 1961-1967
Initial response to the Viennese results
526
533
L-DOPA and depression
Prospects for DOPA therapy in 1967
535
Problems of DOPA therapy in the early 1960s
537

543
XV. THE SECOND COMING: ORAL L-DOPA THERAPY
George Cotzias, manganese and melanin
544
Second International Congress of Neuro-Genetics and Neuro-Ophthalmology (Montréal,
September 1967)
551
Third International Symposium on Parkinson’s Disease (Edinburgh, May 1968) 553
XII

Table of contents

556
L-DOPA: the start of the new beginning
1969: year of confirmation
559
568
L-DOPA in post-encephalitic parkinsonism
Response of physicians, patients and industry to news about L-DOPA 571
574
The Hoffmann-La Roche multicentre trial of L-DOPA therapy
578
The commercial introduction of L-DOPA
585
Industrial production of L-DOPA
587
L-DOPA: the next steps
Official recognition and priority questions regarding L-DOPA therapy 591
Cotzias: further directions
595
597
Problems with L-DOPA therapy
The first “rational therapy” for parkinsonism: Mechanism of the L-DOPA effect 608

XVI. ADJUNCTS AND ALTERNATIVES: THE EXTENSION OF DOPAMINE-
BASED THERAPY
619
Benserazid(e) (Ro 4-4602): the first peripheral decarboxylase inhibitor 620
Carbidopa (MK 485/MK 486)
629
Combination preparations
632
MAO inhibitors: the beginnings
633
MAO inhibitors: the temporary setback
638
MAO-B inhibitors: deprenyl and relatives
641
MAO inhibitors: mechanism of action
650
Chloramphenicol and aberrant mRNA in parkinsonism
657
Apomorphine: the first dopaminergic agonist in antiparkinsonian therapy 658
Piribedil
661
Bromocriptine and other D2 receptor agonists
661
Amantadine
669
Serotonin-related agents
673
XIII

Table of contents

Melanocyte stimulating hormone inhibitory factor
680
Electroconvulsive therapy
681
After 1980
682

XVII. CONCLUDING REMARKS: FROM ALKALOIDS TO NEUROCHEMISTRY 689

[Virginia Therese]

Let me preface this by stating what we all know about PD "meds"...everyone responds/reacts differently so that what I am about to say should be taken in that context. For my pwp, Cogentin was a "nightmare" medication in that she became so cognitively impaired that it caused her to be removed from her position as the medical assistant to a cancer ENT physician for whom she had worked for 22 years. The sad thing about this was that the drug worked remarkably well to alleviate (actually, eliminate) her tremors...actually, had no tremor while taking Cogentin. Doreen actually took on another personality to the point where I did not recognize her as the same person I had known for over 30 years. It was only through my research of this medication that I realized what was happening to her. I contacted her neurologist and he immediately took her off Cogentin. This had to have been the worst period of time since she had been dx'd with PD...and, to this day, Doreen has no recollection of what happened to her while taking Cogentin. As I said...the medication absolutely stopped the tremor so that for someone else, it could very well be an ideal "med" that would not cause the cognitive impairment experienced by Doreen. I merely thought that I would post our experience as a warning to anyone who might be taking Cogentin...or considering taking it...to make you aware of any POSSIBILITY of such a terrible adverse reaction. For those of you who might be taking it..considering taking it..I hope you'll have the good results that this "med" can provide without the horrendous cognitive side effects.

Therese

[ZucchiniFlower]

Hi, I take artane (trihexyphenydyl) along with baclofen for my symptoms. I take as little artane as possible, only 2 mg a day, because it affects short term memory. The balance between dopamine and acetylcholine is important. If too much acetylcholine, symptoms arise. Artane dampens down the acetylcholine. The main Alzheimer's drug does just the opposite, so you can see that acetylcholine is important for memory.

[Jaye]

My neuropsychiatrist is very particular about anticholinergics, as I am stiffness-dominant and at greater risk for dementia than tremor-dominant PWP. If I have a cold I can take Benedryl, but must get off it ASAP. At night I can take ibuprofen (Motrin) for sleep but not Tylenol PM, because it contains Benedryl. If I liked nursing homes, I suppose anticholinergics would be great stuff.

The study found those people who took anticholinergic drugs saw their rate of cognitive function decline 1.5 times as fast as those people who did not take the drugs.
"Our findings point to anticholinergic drugs having an adverse impact on cognitive performance in otherwise normal, older people," said study author Jack Tsao, MD, DPhil, Associate Professor of Neurology at Uniformed Services University in Bethesda, Maryland, and member of the American Academy of Neurology. "Doctors may need to take this into account before prescribing these commonly used drugs."
- American Academy of Neurology (2008, April 22). Using Anti-cholinergic Drugs May Increase Cognitive Decline In Older People.

http://www.sciencedaily.com/releases...0417211539.htm

Jaye

[Jomar]

Google books lets you preview quite a few pages of many books -
here is the link to preview "Beans, Roots, and Leaves" By Paul Bernard Foley

http://books.google.com/books?id=XKS...esult#PPP14,M1

[Dawn Angel]

I am about to embark on a program of taking hyoscyamus niger in an attempt to alleviate the tremors associated with Parkinson's disease. The hyoscyamus niger is sourced from the botanical henbane, from Jade mountain medicine in Ashland, Oregon. The problem with ACP is that titrating in is a tricky process. One has to get the dose just right to reduce tremors without expressing some of the rather nasty side effects. Wish me luck.

Dawn Angel

[krugen68]

Originally Posted by Dawn Angel

I am about to embark on a program of taking hyoscyamus niger in an attempt to alleviate the tremors associated with Parkinson's disease. The hyoscyamus niger is sourced from the botanical henbane, from Jade mountain medicine in Ashland, Oregon. The problem with ACP is that titrating in is a tricky process. One has to get the dose just right to reduce tremors without expressing some of the rather nasty side effects. Wish me luck.

Dawn Angel

Did it work for your tremors ?