Bromocriptine--lisuride cross tolerance.
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Biomedical subjects
Publications and source records attributed to E Parati.
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Madopar, a combination of levodopa with benserazide, induced an inconsistent rise in plasma growth hormone in unmedicated patients with Parkinson's disease and in controls, and a greater growth hormone rise in Parkinsonian subjects on chronic Madopar therapy. In subjects on chronic therapy with levodopa and carbidopa (Sinemet), the growth hormone releasing effect of Madopar was blunted. Madopar increased plasma prolactin (PRL) in controls, unmedicated patients and patients on Madopar therapy while in patients on Sinemet therapy the PRL-releasing effect of Madopar was strikingly reduced. Since these data were interpreted as due to a defective dopamine tone in the hypothalamus of Parkinsonian subjects on Madopar but not Sinemet therapy, a direct dopamine receptor agonist, lisuride was administered. Lisuride, however, elicited a blunted growth hormone response both in patients on Madopar and Sinemet therapy, without revealing a state of supersensitivity of dopamine receptors for growth hormone control in Parkinsonian subjects on Madopar therapy. No difference was present in the PRL-lowering effect of lisuride in the different experimental groups. These findings suggest that: (1) hypothalamic dopamine function is impaired in Parkinsonian subjects on Madopar therapy, preserved in unmedicated patients and enhanced in patients on Sinemet therapy; (2) the endocrine effects observed in Parkinsonian subjects on chronic Madopar therapy may be due to some penetration of benserazide across the blood brain barrier in the region of the hypothalamus; (3) since Madopar and Sinemet are in essence equally effective antiparkinsonian remedies, penetration of benserazide does not occur across the blood brain barrier surrounding the nigrostriatal system.
In this study the author's experience of Parkinson Disease treatment with long-term Bromocriptine (Br) administration, is summarized. Br, which acts directly on dopaminergic receptors, was introduced in combination with L-Dopa and peripheral decarboxylase inhibitors (PDI). The reasons for this association were: 1) the reduced effectiveness of the current treatment (L-Dopa + PDI) 2) onset of AIM (abnormal involuntary movements). 3) patient's desire to try new drugs. Only the patients who had been on the triple association for at least a year, were considered. Therefore of 50 patients originally considered only 19 were included in this study. The addition of Br allowed a reduction of the mean daily dose of L-Dopa(30%) and the therapeutic efficacy of the drug remained unchanged even after more than 4 years treatment. The "on-off" effect and AIM, are reduced by Br especially in the first months of treatment. The triple association is regarded at present as the best treatment for Parkinson disease.
Ten patients affected by various myoclonic syndromes were tested with drugs acting on cerebral serotonin metabolism and with clonazepam (CZP). After L5HTP or serotonergic drugs administration a clear cut improvement was observed in the 2 patients affected by Ramsay-Hunt syndrome, while the patients with myoclonic epilepsy have shown no effect (3 cases) or negative response (1 case). Methysergide was active only in 1 patient affected by progressive erratic myoclonus who had a striking worsening of clinical picture. The main side effects observed were: gastrointestinal distress (L5HTP--4 patients, fenfluoramine--2, quipazine--1, methysergide--2) and cutaneous rash (quipazine--1 case). These results support the possible implication of the serotonergic system in the pathogenesis of myoclonus other than post-anoxic.
A double-blind crossover trial with 2-dimethylaminoethanol (Deanol), a possible precursor of brain acetylcholine, was carried out in nine patients with Huntington's chorea. It was found to be ineffective in inducing any alteration in hyperkinesia.
Twenty-six patients affected by Parkinson's disease were treated with a 2-Br-alpha-ergocriptine (CB 154): 14 cases were given CB 154 alone, and 12 were given CB 154 along with L-dopa plus benserazide (Madopar). Both CB 154 and combined therapy (CB 154+Madopar) induced a significant improvement in total disability score, tremor, rigidity, akinesia, self-sufficiency, and some motor performance tests (dynamic tests). No significant difference was found between results obtained with CB 154 therapy and with Madopar treatment, while the improvement induced by combined therapy (CB 154+Madopar) was significantly higher than that obtained by Madopar alone. The averse reactions caused by CB 154 alone or associated with Madopar are similar to those observed during other dopaminergic treatment. CB 154 alone or combined with Madopar appears to be a useful advance in the management of Parkinson's disease.
Physical stress induces different changes in immune parameters depending on effort schedule and/or customary physical training. The mechanisms whereby they take place and the occurrence of possible tolerance after repeated effort have not been conclusively elucidated. We studied short and medium-term exercise-induced changes in immune parameters after a standard physical effort (24' of cycle ergometer up to the 80% of maximal heart rate, daily for 5 days) in a group of healthy untrained controls. White Blood Cells, lymphocyte subsets, plasmatic catecholamine and cortisol levels, IgG and IL2receptor (IL2R) levels were determined. Most of the observed changes were strictly acute effort-related and disappeared within 3 hours (except for shifts in CD4+ CD45RA+ and CD4+ CD45RA- lymphocytes): they were concomitant to a transient sympathetic activation proved by heart rate (HR) and Norepinephrine (NE) increase. The medium-term effects of repeated daily effort included only a questionable rise in CD19+ and CD3+ CD4- CD8- cells. As far as possible tolerance mechanisms are concerned, we did not detect any change in either the direction or the entity of effort-induced changes in our controls after repeated effort. Study of strictly standardized exercise protocols is mandatory before clinical applications of physical activity in the approach to the treatment of disimmune diseases.