摘要:

Pramipexole is a clinically effective nonergot dopamine agonist. Pramipexole's receptor interactions differ from ergot agonists in several ways. First, it has high selectivity for interacting with dopamine D2 subfamily receptors (D2, D3, and D4receptor subtypes) and has little interaction with adrenergic or serotonergic receptors. Second, within the D2 subfamily, it has preferential affinity for the D3receptor subtype, which, according to preclinical studies, could contribute additional efficacy for treatment of both motor and psychiatric syndromes in Parkinson's disease. Third, it has full intrinsic activity at dopamine D2 subfamily receptors. In addition to pramipexole's unusual receptor profile, whole-animal and cell culture studies suggest that pramipexole might provide neuroprotective effects through depression of dopamine metabolism, antioxidant effects, and stimulation of trophic activity. Pramipexole's demonstrated clinical efficacy for successful treatment in early disease for several years in the absence of L-dopa and as adjunctive therapy with L-dopa in late disease suggests a potential new paradigm for treatment of Parkinson's disease whereby new patients are initiated with pramipexole therapy and L-dopa is added only as necessary.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A new experimental strategy was applied to determine the concentration-effect relation and the therapeutic window of apomorphine in individual patients with Parkinson's disease. Apomorphine was administered by a stepwise intravenous infusion. The infusion rate was increased by 10 μg/kg/h every 20 minutes, up to 100 μg/kg/h or less when adverse effects occurred. Thereafter, the infusion rate was decreased in a stepwise fashion until zero. Plasma apomorphine concentrations were measured every 20 minutes. Clinical efficacy (tapping score and tremor), dyskinesia, and adverse effects were monitored at the same time. The mean clearance of apomorphine was 4.5 L/min (2.2 to 6.6 L/min). Of the 10 patients, 8 responded to apomorphine. The effects were quantal rather than continuous. Within each patient, the concentrations at onset and offset of effect generally were similar. Significant interpatient variability was observed with respect to minimal concentration for each of the effects. Clinical efficacy occurred at a mean minimal effective concentration (MEC) of 4.7 ng/mL (range 1.4 to 10.7 ng/ mL). Dyskinesia was observed at a mean concentration of 8.5 ng/mL (range 2.7 to 20 ng/mL). This value was not significantly different from the MEC. The mean minimal toxic concentration was 16.7 ng/mL (8.5 to 24.5 ng/mL) and was significantly different from the mean MEC. In conclusion, the stepwise increase and decrease of the intravenous infusion rate is a suitable tool for the establishment of the concentration-effect relation of apomorphine in individual patients. The finding of a narrow therapeutic window, in which the onset concentrations vary from patient to patient, underlines the need for accurate and individualized dosing.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The phamacokinetics and metabolism of R-apomorphine were determined in 10 patients with idiopathic Parkinson's disease after intravenous infusion of 30 μg-kg-1in 15 min. Specifically, emphasis was on enantiomeric interconversion into S-apomorphine and on the formation of apocodeine and isoapocodeine, since these metabolites may interfere with the pharmacodynamics of R-apomorphine. The pharmacokinetics of R-apomorphine in plasma were determined using an enantioselective highperformance liquid chromatography assay. In most patients, the plasma concentration versus time profile was characterized by a biexponential function. The values of relevant pharmacokinetic parameters were as follows: clearance 40 ± 15 ml min-1kg-1, volume of distribution at steady state 1.6 ± 0.5 1.kg-1, and terminal half-life 41 ± 13 min. No measurable concentrations of S-apomorphine were detected in plasma, indicating that enantiomeric interconversion does not occur in vivo. Furthermore, no measurable concentrations of the methylated metabolites apocodeine and isoapocodeine could be detected in plasma. The metabolism of apomorphine was characterized on basis of the excretion of unchanged R-apomorphine, S-apomorphine, apocodeine, isoapocodeine, and their respective sulfate and glucuronide conjugates in urine. The total excretion of unconjugated S-apomorphine, apocodeine, and isoapocodeine was less than 0.1% of the administered dose. The total excretion of unchanged apomorphine, apomorphine sulfate, and apomorphine glucuronide amounted to 0.3 ± 0.4%, 3.8 ± 1.% and 6.0 ± 2.2% of the administered dose, respectively. The findings of this study show that on intravenous administration, S-apomorphine and the metabolites apocodeine and isoapocodeine are unlikely to interfere with the pharmacologic actions of R-apomorphine in patients with idiopathic Parkinson's disease. Furthermore, no pharmacokinetic interaction between R-apomorphine and catechol-O-methyl transferase inhibitors is expected.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Ropinirole is a novel, nonergoline, selective D2-type dopamine agonist developed to treat Parkinson's disease. Safety data from therapeutic studies involving 1364 patients receiving ropinirole are reported (mean daily dose 8.7 mg, early therapy; 8.2 mg adjunct therapy). In early therapy, the emergent adverse experiences more common with the ropinirole group compared with placebo were nausea, somnolence, leg edema, abdominal pain, vomiting, dyspepsia, and hallucinations. In adjunct therapy, they were dyskinesia, nausea, hallucinations, and confusion. Most adverse experiences were mild and associated with a similar withdrawal rate compared with the placebo group. Except for hallucinations, the incidence of emergent adverse experiences decreased with time, despite increasing doses. Long-term adverse experiences particularly associated with ergoline-type dopamine agonists have so far not been observed with ropinirole. Only 1.2% of patients receiving ropinirole developed dyskinesia compared with 11.2% receiving L-dopa in early therapy over a mean period of 17 months. There were no clinically significant changes in cardiovascular parameters or laboratory data. The incidence of adverse experiences in the bromocriptine group was low, possibly because of a slow titration scheme and low average dose. Overall, the safety profile of ropinirole appears similar to that of other dopamine agonists. Clinical studies are continuing to assess the long-term safety and efficacy of ropinirole.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Case reports and studies of other neuroleptics suggest the efficacy of risperidone in the treatment of mania. Forty-five inpatients with DSM-IV mania were studied in a 28-day randomized, controlled, double-blind trial of either 6 mg daily of risperidone, 10 mg daily of haloperidol, or 800 to 1200 mg daily of lithium. The patients in all three groups showed a similar improvement on the total score for all rating scales at day 28 (Brief Psychiatric rating scale: lithium 9.1, haloperidol 4.9, risperidone 6.5, F = 1.01, df = 2,p= 0.37; Mania rating scale: lithium 15.7, haloperidol 10.2, risperidone 12.4, F = 1.07, df = 2,p== 0.35 [analysis of variance]). The Global Assessment of Functioning and Clinical Global Impression data showed a similar pattern of improvement. This study suggests that risperidone is of equivalent efficacy to lithium and haloperidol in the management of acute mania. The extrapyramidal side effects of risperidone and haloperidol were not significantly different.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

There is strong evidence to support the hypothesis that the rapid effects of steroids on neurons are membrane-mediated. Rapid steroid effects have been demonstrated in the absence of intracellular receptors, in the presence of RNA or protein synthesis inhibitors, and in response to steroids coupled to large proteins that block access to intracellular receptors. This study selectively reviewed the emerging body of evidence suggesting that steroids have multiple sites of cellular actions, and explored in depth one possible membrane-mediated mechanism of action, the membrane-intercalation model.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In this article, the authors examine the effect of lisuride on 22 patients with probable Alzheimer's disease (NFNCDS/ADRDA criteria) in a randomized double-blind, placebo-controlled, parallel group design. Ten patients received lisuride and 12 patients received placebo. Lisuride was administered in a dose-finding phase of four weeks and an efficacy phase of eight weeks, with a maximum dose of 0.3 mg daily. Outcome measures included global clinical impression, general cognitive function, mood, verbal and visual memory, attention, and psychomotor function. Average decline in Mini-Mental Sate Examination score after 12 weeks treatment was less often statistically significant in lisuride treated patients than in patients receiving a placebo (p < 0.05). Patients treated with lisuride improved their average total score and short-delay cued recall score on the California Verbal Learning Test, a test of verbal memory, whereas placebo-treated patients showed worse performance compared with baseline. These differences approached statistical significance, with p = 0.06 and p - 0.05, respectively. No other differences between the treatment groups were evident. The authors failed to find a consistent effect of lisuride on symptoms of Alzheimer's disease. However, this study's sample size was relatively small, and larger studies are needed to ascertain the treatment effects of serotonergic antagonists on Alzheimer's disease.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Spasmodic dysphonia (SD) is at present defined as focal dystonia. Botulinum toxin (BT) injection is the treatment of choice for SD. BT is usually injected by a percutaneous route, but a direct, visually guided transoral approach has also been successful. It is not known whether percutaneous injection is as effective as the transoral approach. This article reviews our experience with both techniques of injection on 29 patients with adductor type SD. Since 1992, we have carried out 48 treatment sessions with the transoral technique and 76 treatment sessions with the percutaneous technique. Two patients did not respond to the percutaneous technique despite several attempts, but they did respond to the transoral approach. Globally, transoral technique was superior to percutaneous technique in terms of effectiveness (48 of 48 responses with transoral technique versus 61 of 76 responses with percutaneous approach, p < 0.01). Dosage of BT, duration, and side effects were similar with both techniques. This article also describes a simple, inexpensive device, composed of materials on hand at every hospital, that facilitates the transoral approach.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Hemifacial spasm features myoclonie-like, paroxysmal, unilateral muscle twitching, attributable to vascular compression at the facial pontine root entry zone. We present the case of an 85-year-old man who presented with idiopathic hemifacial spasm with onset 23 years before. For the last 5 years, he was successfully treated with botulinum toxin injections. However, occasional nitrate intake for precordial pain promptly triggered muscle twitching. Vasodilation may exacerbate not only cases of hemifacial spasm, but even of trigeminal neuralgia, both recognized as neurovascular compressive syndromes.

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1998

数据来源: OVID