摘要:

One of the biotechnology fields which is beginning to have a significant impact upon neuropharmacology is that of new drug delivery systems. In recent years, drug delivery technology has made some exciting strides beyond the traditional forms of drugs in tablets and capsule form or parenteral injection formulations. New drug delivery systems are being developed to achieve rate-controlled, targetted delivery to the CNS to ensure not only that a therapeutic agent gets into the CNS, but that it does so at the right dose, and at the desired rate. Here we review some of the advances in modern drug delivery technology which have recently become available for clinical applications in the field of neurology.

ISSN:0362-5664    

出版商:OVID    

年代:1988

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Summary:Four parkinsonian patients received continuous duodenal infusions of levodopa (LD) for severe “on-off” phenomena associated with Sinemet (carbidopa/levodopa) therapy. All patients had marked decreases in motor fluctuations on the infusions compared with tablets. Two factors that appear related to this improvement are the ability of duodenal infusions to produce steadier plasma LD concentrations and/or to maintain LD concentrations above a minimum threshold needed to achieve the “on” state.

ISSN:0362-5664    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Summary:Deprenyl, a selective inhibitor of monoamine oxidase, type B, which is free of the “tyramine effect,” may ameliorate symptom fluctuations in advanced Parkinson's disease (PD). We randomized 96 patients with marked symptom fluctuations at three centers to receive either deprenyl 5 mg b.i.d. or placebo in parallel fashion in addition to a previously optimized levodopa/carbidopa (Sinemet) regimen. Disability was recorded hourly at home by patients 3 days weekly during the 2-week baseline and the 6-week treatment period. Disability during the “on” state was assessed each week by examination. Mean hourly self-assessment of gait improved in 28 of 50 patients (56%) receiving deprenyl (mean degree of improvement 0.25 points on a 0–2 scale) and in 14 of 46 (30.4%) taking placebo (mean 0.15). Mean hourly overall symptom control improved in 29 (58%) taking deprenyl (mean 0.34) and in 12 (26.1%) taking placebo (mean 0.15) (p < 0.01 for each parameter). No significant improvement occurred in the objective quality of the “on” state with deprenyl. Mean daily Sinemet dosage decreases were 17% in the deprenyl group and 7% in the placebo group. Adverse effects included nausea, light-headedness, dyskinesias, and hallucinations, all of which abated after the Sinemet dose was reduced. We conclude that deprenyl is of moderate benefit in a majority of patients with symptom fluctuations complicating PD and is generally well tolerated.

ISSN:0362-5664    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Summary:Local pharmacological manipulations of both pupils in persons with cluster headache (CH) have shown a reduced pain-side sympathetic activity. It is difficult to determine if this sympathetic defect is localized in the nuclei of the CNS and/or in peripheral neurons that innervate the pupil. This study demonstrates that in a CH group 2% tyramine (an intraneuronal norepi-nephrine releaser) instillation into both eyes induces an asymmetric and bilateral mydriasis with the onset of anisocoria characterized by a pupillary diameter being less on the pain-side eye. In addition, intravenous administration of 0.10 mg clonidine, an inhibitor of central sympathetic activity, causes a bilateral miotic response, which is more marked on the pain-side eye. In a healthy control group, clonidine induces a symmetric and bilateral miosis but less intense than that observed in both eyes of CH sufferers. In CH patients, pretreatment with clonidine augments the degree of anisocoria induced by tyramine instillation, increasing the mydriatic response only in the pain-free-side pupil. The hypothesis of a permanent sympathetic defect of the pain-side pupil expressing itself as a reduced sympathetic tone of CNS nuclei and peripheral neurons that innervate the pupil is proposed.

ISSN:0362-5664    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Summary:For assessment of the underlying central mechanisms of interferon (IFN), measurements have been made of the neurotoxicity, cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) concentrations, along with electroencephalographic (EEG) recordings and visual evoked potentials (VEP) during recombinant IFN-γ therapy. Interferon-γ was administered intravenously to 14 patients with non-small-cell lung cancer as 2 mg/m2(48 ± 106IU/m2) three times weekly with 4 h infusion for 12 weeks. The cerebrospinal fluid (CSF) samples were taken by means of lumbar puncture prior to treatment and during the end of the second week of IFN-γ infusions. During the course of treatment, CSF 5-HIAA diminished from 129.6 ± 10.9 to 84.5 ± 10.4 nmol/L (p < 0.001), while no significant changes were observed in HVA, EEG, and VEPs. These results suggest that IFN-γ has an effect on the central serotonergic neurotransmission.

ISSN:0362-5664    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Summary:Objective quantification of the symptoms of Meige's syndrome is difficult and has not been performed in the majority of pharmacological studies of Meige's syndrome published so far. The aim of the present study was to reexamine the therapeutic potential of biperiden, clonazepam, haloperidol, and lisuride using an objective method of quantification of the symptoms. Eleven patients received daily i.v. injections of biperiden, 5.0 mg; clonazepam, 1.0 mg; haloperidol, 2.5 mg; lisuride, 0.05 mg; and placebo in randomized order. The symptoms of the patients [idiopathic blepharospasm (IB), in 11 patients, oromandibular dystonia (OMD) in four patients] were quantified by a blind observer counting the frequencies and recording the cumulative duration of sustained spasms of IB and OMD over periods of 4 min before, and 15, 30, 60, 90, and 120 min after the i.v. challenges. Baseline quantification of IB and OMD was performed at identical intervals on randomized days of the trial. Significant improvement of the IB scores was found in response to biperiden and clonazepam and a trend toward improvement in response to lisuride (Wilcoxon test). Evaluation of the individual IB scores of each patient following the various drug challenges failed to predict the therapeutic potential of these drugs for subsequent oral treatment.

ISSN:0362-5664    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Summary:Loss of efficacy and response fluctuations develop in many patients with Parkinson's disease after long-term levodopa therapy. This may be due in part to near-total degeneration of the surviving nigrostriatal dopaminergic neurons during disease progression, with massive decreases in the capacity of the striatum to form and store dopamine from exogenous levodopa. It was recently suggested that intracerebral grafting of fetal nigral or adrenal chromaffin cells may be beneficial in advanced Parkinson's disease by reestablishing spontaneous dopaminergic neurotransmission or by secretion of trophic factors that promote sprouting of residual dopaminergic nerve-terminals. It is now hypothesized that intrastriatal transplantation of such cellular elements that contain the enzyme dopa decarboxylase and dopamine storage sites may significantly increase synthesis, storage, and release of dopamine from exogenous levodopa. It may therefore reverse loss of responsiveness and restore the initial smooth and stable beneficial effect of levodopa therapy.

ISSN:0362-5664    

出版商:OVID    

年代:1988

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Akathisia is an often distressing disorder characterized by a feeling of inner restlessness associated with a compulsion to move (1). It is best recognized as a side effect of antipsychotic drugs. Not surprisingly, much of the material published about this peculiar phenomenon can be found in psychiatric literature. However, the occurrence of akathisia need not be limited to that particular patient population. We report akathisia as a result of methysergide administration.

ISSN:0362-5664    

出版商:OVID    

年代:1988

数据来源: OVID