A year's comparison of treatment of patients with parkinson's disease with levodopa combined with carbidopa versus treatment with levodopa alone.
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Biomedical subjects
Publications and source records attributed to C D Marsden.
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1. The pA2 anti-acetylcholine activity in vitro for benapryzine was 6.55 compared with 9.02 for benzhexol.2. In vivo, the anti-acetylcholine activity of benapryzine relative to benzhexol was 0.038 as assessed by the mydriatic response of mice after subcutaneous administration. The relative activity assessed by the inhibition of pilocarpine-induced salivation was 0.13 after oral administration and 0.056 following subcutaneous administration of the drugs.3. Benapryzine had the same order of activity as benzhexol in inhibiting oxotremorine-induced tremors in mice.4. Benapryzine had anticonvulsant properties but no analgesic activity, whilst in high doses it antagonized the extrapyramidal symptoms induced by perphenazine in rats.5. In patients benapryzine was effective in reducing the symptoms of Parkinson's disease without overt anti-cholinergic effects or central hallucinogenic actions.6. Benapryzine abolished the excess tremor and reduced the rigidity and akinesia induced by physostigmine in Parkinsonian subjects.
Thirty patients with Parkinson's disease were treated for four weeks with levodopa combined with an inhibitor of extracerebral dopa decarboxylase, L-alpha-methyldopahydrazine (MK 486). The therapeutic results were compared with the effects of treatment of a group of 40 patients with levodopa alone. Patients treated with the combined therapy improved more rapidly, had less nausea and vomiting, and required a much smaller dose of levodopa than patients treated with levodopa by itself.
The effects of slow withdrawal of anticholinergic medication and addition of benzhexol (8 mg/day) have been studied in patients with Parkinson's disease on stable levodopa therapy. Withdrawal of anticholinergic drugs led to measurable and often severe deterioration in about two-thirds of patients. Addition of benzhexol produced a slight but definite additional improvement in those patients in whom anticholinergics were withdrawn before the trial. Anticholinergic drugs thus still have a part to play in the treatment of Parkinson's disease, for they produce benefit in addition to that provided by levodopa.
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Of 106 patients admitted for investigation to a neurological hospital with a presumptive diagnosis of dementia, 84 were confirmed to have intellectual impairment or loss of learning and memory function or both. A possible aetiology for the dementia was found in 36 of these 84 patients; the commonest causes discovered were intracranial mass lesions, arterial disease, and alcoholism. Fifteen of the 106 patients were found not to be demented but to have some other illness, most commonly depression. Of the whole series some 15% of the patients suffered from conditions that were amenable to treatment.
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