ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Thirteen parkinsonian patients drawn from two large parkinsonism clinics experienced hypersexuality as a consequence of anti-parkinsonian therapy. The cases include only those whose sexual behavior on treatment became a concern to the patient's family or a social agency. The majority of patients were men and had a relatively early onset of parkinsonian symptomatology. There was no relation between functional improvement and increased sexuality. Most patients showed some element of dose dependency between antiparkinsonian drugs and the hypersexual behavior. Prior sexual profile included from no sexual outlet to hypersexuality. Neither the prior history of psychiatric illness nor brain damage predisposed to such response on treatment, and in most patients, it was not a part of hypomania or a more diffuse psychiatric disturbance. We propose that hypersexuality on antiparkinsonian drugs is consequent to inhibition of prolactin secretion.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The relationships between magnitude of response to orally administered carbidopa/levodopa (CD/LD) and serum/cerebrospinal fluid (CSF) concentrations of levodopa (LD), 3-O-methyldopa (3-O-MD), and homovanillic acid (HVA) were studied in 15 patients with chronic LD-treated Parkinson disease. The degree of clinical benefit derived from a 25/250 tablet of CD/LD could not be correlated with absolute serum levels of LD, 3-O-MD or LD/3-O-MD ratios. CSF levels of LD and 3-O-MD were also not associated with improvement. CSF levels of HVA, however, did significantly correlate with magnitude of response to LD. Furthermore, CSF HVA levels were not dependent on previous LD dosage. Our data suggest that in chronic LD-treated patients, central factors related to the integrity of the nigrostriatal tract may be a more important determinant of magnitude of response to LD than peripheral elements affecting the amount of LD entering the central nervous system.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Prodrugs may be used to improve the absorption and bioavailability of certain active compounds. We have examined the ability of a novel catechol monoester of L-DOPA, NB-355 [L-3-(3-hydroxy-4-pivaloxyloyphenyl)alanine], to stimulate locomotor activity and induce dyskinesias in MPTP-treated primates. In the presence of carbidopa, a dose-dependent increase in locomotor activity over 41/2h was observed following administration of L-DOPA (10, 20 or 40 mg/kg p.o.) or NB-355 (20, 40 or 80 mg/kg p.o. dopa equivalent). The doseresponse curve for NB-355 was shifted to the right such that approximately twice the dopa equivalent dose of NB-355 was required to stimulate locomotor activity to the same level observed for L-DOPA. At doses matched for total locomotor stimulation over the 41/2-h period (20 mg/kg L-DOPA and 40 mg/kg NB-355), there was a more gradual rise and increase in the duration of motor stimulation by ∼40% using NB-355. At these doses, drug-induced dyskinesias were less severe following treatment with NB-355 than with L-DOPA. Our findings suggest that NB-355 may be a useful therapeutic agent for increasing the duration of action of L-DOPA and reducing the severity of peak-dose dyskinesia.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In this study, the hemodynamic and neurochemical effects of lisuride, a dopamine agonist with serotoninergic properties, have been evaluated in de novo parkinsonian patients and in elderly subjects with mild cognitive impairment. Blood pressure (BP), heart rate (HR), and urinary catecholamine (CA) fluctuations throughout the 24-h cycle were monitored before and during lisuride therapy along with BP, HR, and plasma CA responses to the tilt-table test. Lisuride (1.2–2.4 mg/day) administered in an open-type 15-day study was capable of decreasing the urinary CA excretion and norepinephrine plasma levels in parkinsonian patients. In some cases, the cardiovascular response to standing was impaired. Lower doses of the drug (0.15 mg/day), administered to elderly patients in a double-blind parallel group vs. placebo study, did not induce any change in cardiopressor responses but decreased the 24-h urinary excretion of epinephrine. These results suggest the importance in both conditions of detecting early stages of alterations in cardiopressor homeostatic processes before therapy with DAergic drugs is initiated.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

In an open-label study, glycine was administered orally (10.8 g/day in three divided doses) to six chronically psychotic patients, as an adjunct to conventional neuroleptic therapy, for periods extending from 4 days to 8 weeks. Glycine was administered in an effort to facilitate endogenous glutamatergic transmission at the level of theN-methyl-D-aspartate (NMDA) receptor complex, since a glutamatergic deficiency in the pathophysiology of schizophrenia has been postulated. Therapeutic efficacy was assessed with standardized psychiatric rating scales. Beneficial effects on behavioral symptomatology were observed in two patients, whereas two others worsened. In one of the two responders, clinical deterioration occurred after glycine withdrawal consistent with a positive adjuvant effect in this patient. However, glycine rechallenge in this patient was not associated with the clinical improvement seen during the initial glycine period. Clinical worsening was not observed after glycine discontinuation in the second responder. Glycine administration reduced neuroleptic-induced muscle stiffness and extrapyramidal dysfunction in three of the six patients. All patients tolerated the clinical trial. The limited penetrability of glycine across the blood-brain barrier is a major limitation of this approach to facilitating glutamatergic transmission at the level of the NMDA receptor complex.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effect of pharmacologie denervation of striatal tissue on the production of growth promoting factors was examined in a cell culture system. Relative to saline-treated controls, rats were rendered behaviorally hypersensitive to a subsequent apomorphine challenge by 2 months of chronic treatment with haloperidol. Four days following chronic treatment, the animals were killed and the striata and cerebella were homogenized in Hank's Balanced Salt solution. The supernatants of these crude homogenates were then added to E-13 rostral mesencephalic tegmentum cultures for 6 days. Within 24 h, the haloperidol-treated striatal supernatants induced an overt increase in culture growth relative to all other supernatants. After 6 days, cultures incubated with haloperidol-treated striatal supernatants exhibited a significant increase in dopamine and GABA uptake relative to cultures incubated with all other supernatants. This effect was observed in the presence and absence of glia. The relative degree of this increased uptake was dependent upon the amount of haloperidol-treated striatal supernatant added. Boiling the supernatant removed the growth promoting effect. These results suggest that pharmacologic denervation of striatal tissue leads to a “target-specific” increase in growth promoting activity that may play a role in the pharmacologie and behavioral effects of haloperidol.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

trans-Dihydrolisuride, a partial dopamine receptor agonist, was tested for its effects on chorea in a double-blind, crossover clinical study in 10 patients with Huntington's disease. In eight patients, a neurophysiological evaluation was also performed. No reduction in choreic movements or improvement in voluntary movement performance was observed. However, in some patients, there was a slight improvement in patients' alertness and a reduction of the movement reaction time.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The administration of bromocriptine in addition to levodopa in Parkinson's disease produces beneficial results. Several hypotheses have explained the advantage of the combined treatment by a pharmacodynamic interaction in the striatum. However, no study has considered the possibility that levodopa modifies the kinetics of bromocriptine. In the present study performed with parkinsonian patients, we measured blood levels of bromocriptine (by radioimmunoassay) at 0, 30, 60, 90, 120, 180, and 240 min after the oral administration of bromocriptine alone and together with 250 mg levodopa plus 25 mg DCI. After loading of bromocriptine alone, we found mean peak levels at 60 min (1.42 ng/ml) and at 90 min (1.82 ng/ml). These values were reduced by levodopa (0.97 ng/ml at 60 min and 0.93 ng/ml at 90 min). Although we did not observe substantial clinical differences among the groups after the drug challenge (Webster scale), this study supports our previous findings and suggests that one of the advantages of a combined treatment may result from a modification of the plasma levels of bromocriptine by levodopa. A “smoothing” of the plasma bromocriptine curve possibly avoids sudden oscillations of the drug and enables a more “stable” penetrability of the medication into the central nervous system. Therefore long-term combined treatment is advised in preference to bromocriptine alone.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The conventional dose of deprenyl used in Parkinson's disease is 10 mg/day, having been established by in vitro platelet studies and clinical evaluation. Twelve patients with Parkinson's disease on treatment with L-dopa who showed evidence of wearing-off effects or motor oscillation were studied in a double-blind, placebo-controlled, crossover trial to compare conventional doses of deprenyl with higher doses (up to 40 mg/day) and placebo. We did not find higher doses of deprenyl to be superior to conventional doses and in 17% of cases treatment had to be withdrawn because of side effects.

ISSN:0362-5664    

出版商:OVID    

年代:1989

数据来源: OVID