Biomedical subjects
Publications and source records attributed to G M Stern.
The clinical pharmacology concerned in the evolution of deprenyl as an adjuvant in the treatment of Parkinson's disease is briefly reviewed, with an assessment of its therapeutic potential. Experiments to clarify its mode of action are described, indicating that its clinical effects do not depend upon its amphetamine metabolites.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Gait and mobility of 50 Parkinsonian patients were studied using an instrumented walkway and by analysis of video tape. Whilst walking velocities did not differ from those of subjects with other conditions affecting gait, worsening of the patients' clinical condition was related to deterioration of scores in these objective tests.
The progress of 50 previously untreated patients with idiopathic Parkinson's disease taking maximum tolerated doses of bromocriptine is described. Twenty-eight showed sustained benefit, defined as a 25% improvement in disability scores for at least 1 year, and in five this improvement persisted for longer than 5 years. However, there was a tendency for deterioration to occur after about 2 years of bromocriptine. Fewer of the late complications associated with levodopa therapy were seen in those taking bromocriptine, and drug-induced dyskinesia was seen in only one patient. Fourteen early bromocriptine failures subsequently responded well to levodopa, but the addition of levodopa to patients showing late deterioration on long-term bromocriptine was unsuccessful. These results indicate that the total duration of effective drug treatment for Parkinson's disease cannot be extended by giving bromocriptine before commencing levodopa.
Forty-four previously untreated patients with early idiopathic Parkinson's disease were treated from the time of diagnosis with submaximum doses of levodopa (mean 420 mg) in combination with a peripheral dopa decarboxylase inhibitor and followed for a minimum period of 3 years. Forty-one gained initial worthwhile improvement, and 17 achieved a reduction in pretreatment disability scores of more than 50%. After 3 years of sustained therapy, only 14 had completely maintained their initial response, and 12 patients were experiencing end-of-dose deterioration; 13 patients had mild peak-dose dyskinesias, but none developed the on-off phenomenon, hypotonic freezing, or end-of-dose dystonia. Retrospective comparison with patients matched for duration of disease and pretreatment severity who had been given maximum tolerated doses of levodopa (a comparable mean dose of 950 mg) showed that the smaller dose regimen reduces peak-dose dyskinesias but not waning of response or end-of-dose deterioration.
Explore the source record for details and available documents.
Although (-)-deprenyl is known to be metabolized to methamphetamine and amphetamine, two small-scale double-blind trials indicate that neither metabolite contributes to all therapeutic benefit conferred by this drug in certain patients with Parkinson's disease: the manipulation of urinary pH, which alters the rate of excretion of these metabolites, failed to change the response pattern; substitution of a metabolite mixture for active drug caused a falling off in benefit.
Twenty-one patients with Parkinsonism secondary to von Economo's encephalitis were typed for HLA-A, B, C and DR antigens. No differences were found in the phenotype frequencies of these antigens compared with controls. This finding fails to support the hypothesis of genetic susceptibility to post-encephalitic Parkinsonism.
In a group of six Parkinsonian patients and 13 "controls" with non-Parkinsonian neurological disease, there was a high correlation between both free and conjugated phenylacetic acid concentrations in plasma and cerebrospinal fluid taken at about the same time. This compound is the major metabolite of phenylethylamine, the production of which may be disturbed in a number of neuropsychiatric illnesses. Thus plasma measurements might be employed clinically to provide an estimate of central changes in phenylethylamine economy. A small but significantly higher proportion of conjugated phenylacetic acid was present in the plasma (but not cerebrospinal fluid) of Parkinsonians compared with controls.
In a case control study of the relationship between smoking habits and Parkinson's disease a negative association was demonstrated with a relative risk of 0 x 52. A history of smoking up to 20 years earlier was associated with a risk of developing Parkinson's disease equal to about half that in non-smokers. The type of disease, age of onset and rate of progression were associated with a similar reduction in risk implying that in respect of smoking history the disease is homogeneous. The positive correlation of degenerative vascular disease with smoking is further evidence that arteriosclerosis is not involved in the causation of Parkinson's disease. The negative association between Parkinson's disease and smoking is confirmed and is independent of other associated factors. The known and serious risks of smoking far outweigh the possible benefit of lowered risk of Parkinson's disease.
Explore the source record for details and available documents.
The selective monoamine oxidase (MAO) B inhibitor (-)deprenyl failed to produce any greater benefit than placebo in a limited double-blind trial conducted in depressive patients. Its relative freedom from the so-called cheese effect was confirmed, however, in drug-treated patients challenged IV with tyramine. There is evidence to suggest that this cheese effect, a facilitated tyramine-induced hypertensive response, is pharmacologically distinct from MAO inhibition proper. Thus, it is conceivable that its central counterpart, an enhanced noradrenaline release due to the access of traces of tyramine to the CNS, is a prerequisite for any therapeutic benefit obtainable with the MAO-inhibitory drugs in general.
The progress of 50 previously untreated patients with idiopathic Parkinson's disease taking maximum tolerated doses of bromocriptine is compared with patients who had taken levodopa. Twenty-eight of the bromocriptine treated patients showed sustained benefit for at least one year and in five this persisted longer than five years. Fewer of the late complications of levodopa therapy occurred in those taking bromocriptine; drug-induced dyskinesia was seen in only one patient and oscillations in performance were not observed. There was a tendency for deterioration to develop after two years treatment when patients then failed to respond well to levodopa. It was not possible to extend the period of effective control of disabilities by first giving bromocriptine.
Explore the source record for details and available documents.
The clinical features of akinetic freezing occurring in a group of 85 patients with idiopathic Parkinsonism and the individual methods used to overcome immobility are described. Frequency and severity of attacks are related to duration of disease and are not amenable to currently available medications. The pathogenesis and therapeutic implications are briefly discussed.
The effect of (-)-deprenyl, a rapidly acting selective monoamine oxidase (MAO) B inhibitor, on the sleep and mood of six healthy young male adults was investigated. The drug was administered double-blind in a balanced cross-over design. The dose (5-10 mg/day for 3 days) was chosen to cause complete inhibition of MAO, a process which usually takes 1-2 weeks with conventional MAO inhibitors. The inhibition was monitored by measuring platelet MAO activity and phenylethylamine excretion. Urinary phenylethylamine concentration was raised in all subjects. Subjects were unaware of any sleep disturbance due to the drug although the electroencephalogram (EEG) showed increased wakefulness. The onset of rapid-eye-movement (REM) sleep was delayed and the total amount reduced; the amount of stage 2 sleep was increased. The only effect of the drug on mood was to decrease the level of alertness prior to sleep. There was a slight but significant increase in the pre-sleep systolic blood pressure. There were no effects due to drug withdrawal.