摘要:

SummaryFelbamate, 2-phenyl-1,3-propanediol dicarbamate, is an antiepileptic drug recently approved by the United States Food and Drug Administration. It has a novel mechanism of action whereby it may decrease excitation by inhibiting glycine binding at the NMDA receptor, and it appears to have neuroprotective properties in addition to antiepileptic ones. A number of animal models have demonstrated felbamate to have a broad range of efficacy as well as a favorable safety profile. In humans it has been potentially linked to some cases of aplastic anemia. It is effective in the treatment of partial and secondarily generalized tonic-clonic seizures as well as seizures associated with the Lennox-Gastaut syndrome, especially drop attacks. It may also be effective against atypical absence as well as other seizure types. Felbamate monotherapy is generally well tolerated, with such side effects as insomnia and anorexia occurring most commonly. Felbamate shows great promise as a useful antiepileptic drug, but its role in clinical practice awaits further investigation of recently reported cases of aplastic anemia.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryEpilepsy and CNS injury identify a heterogenous group of diseases, many of which exhibit refractoriness (e.g., the partial epilepsies) to established drug therapy or, as in the case of brain and spinal cord injuries of variable etiologies, remain a formidable target for successful drug development. As such, the search for safe, effective antiepileptic and neuroprotective drugs continues. Although several CNS targets have been identified for drug development, especially the excitatory amino acid receptors, free-radical systems, gangliosides, and nitric oxide, etc., the opioid system and its diversity of receptors have, until recently, received little attention. This review attempts to focus on one opioid system, namely the kappa receptor class of opioid ligands, specifically addressing the potential anticonvulsant and neuroprotective properties of the arylacetamide series of kappa opioid analgesics as novel pharmacotherapeutic approaches to the treatment of epilepsy, stroke, or trauma related brain or spinal cord injury.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThe mechanism of action of flunarizine (FZ) and cinnarizine (CZ) on the CNS is not fully understood. Computer analysis of saccadic eye movements (SEM) provides a sensitive and objective method for evaluating drug effect on the function of specific brain structures. This study aimed to assess the effect of a single oral dose of FZ (20 mg) and CZ (150 mg) on CNS function by means of computer analysis of SEM. Ten healthy volunteers were studied according to a double-blind, cross-over, placebo-controlled design. Peak saccadic velocity (PSV), which is related to the function of a specific group of burst neurons located in the brain stem, was significantly reduced by FZ. No significant effect of FZ on saccade accuracy (SA) and saccade latency (SL) was found. CZ did not produce significant effects on SEM, but a trend to decrease PSV. The possibility that a FZ central effect may be related to a stabilizing action on burst activity of neurons is discussed.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryRecently, there has been some evidence suggesting that exposure to neuroexcitotoxic amino acids, culminating in excessive neuronal calcium influx, may cause nerve cell destruction in motor neuron disease (MND). We therefore hypothesized that central calcium channel blockade with nimodipine might slow-down progression of MND. Two patients with sporadic MND were treated in a double-blind placebo controlled cross-over study with oral nimodipine (120 mg/day) for 5 months. Disease progression was assessed by repeated computerized measurements of isometric force from 20 muscle groups, and calculation of global force score. Global force deterioration slopes during the 5-month periods of nimodipine or placebo therapy were highly linear and almost identical. Nimodipine therefore does not seem to be effective in changing the course of MND. The observed remarkable linearity of disease course also confirms that cross-over methodology and serial measurements of muscle force are constructive tools in the clinical evaluation of novel therapetic strategies for this devastating disease.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThe pharmacokinetics of the clinically determined optimal dose of controlled release levodopa/carbidopa 25/100 (Sinemet CR 25/100) after 12 weeks of therapy was studied in nine parkinsonian patients without prior exposure to levodopa. The pharmacokinetics of single oral doses of controlled release levodopa/carbidopa 25/100 and 50/200 were also compared. As predicted from the plasma half-life (1.7 ± 0.3 h) and confirmed by morning trough levels, levodopa did not accumulate when controlled released levodopa/carbidopa 25/100 was administered twice daily. The absorption and bioavailability of CR 25/100 are minimally greater than CR 50/200. Controlled released levodopa/carbidopa 25/100 levodopa plasma levels peak slightly faster than controlled release levodopa/carbidopa 50/200.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThe beneficial effect of bromocriptine in fluctuating Parkinson's disease (PD) under chronic levodopa therapy has been reported to be lost in the long term in most patients. We attempted slow bromocriptine discontinuation in nine PD patients to whom this drug have been added to levodopa because of fluctuating motor responses but who appeared to cease benefitting from this association after an average of 4.6 years (range, 1.3–8 years) of sustained bromocriptine therapy. Bromocriptine was discontinued by gradually tapering off the dosage (mean, 8.5 mg/week) while leaving levodopa medication unchanged. The percentage time spent “off” during waking hours increased in all patients (average, 30.2 ± 18.5% versus 65.6 ± 82.6%, p < 0.001) and in three patients the “on-off” pattern shifted from random fluctuations to disabling “off” periods 23–26 times longer than before discontinuation. Sustained bromocriptine therapy does not prevent the continuous deterioration of motor fluctuations. However, we believe that this drug remains partially effective over the long term and should not be discontinued in PD patients with uncontrolled fluctuations, even though their condition may actually appear to worsen as compared to when bromocriptine therapy was first started.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryApomorphine (0.5 mg/kg) was administered subcutaneously and percutaneously to rabbit in order to compare the pharmacokinetic data obtained according these two different routes. For the percutaneous administration, an apomorphine gel was prepared by dissolution of apomorphine in an hydroxypropylmethylcellulose gel of medium viscosity. The evaluation of plasma levels after percutaneous route showed an absorption in all the animals. The time to peak plasma concentration (29.4 ± 7.8 min) was close than after the subcutaneous route (25.8 ± 4.9 min). The absorption of apomorphine was of 90% at minute 68 and minute 321 min after the subcutaneous and the percutaneous route, respectively. The peak plasma concentration and the area under the curve were significantly greater with the subcutaneous route. The bioequivalence of the percutaneous route was 35% of the subcutaneous administration. Those data suggested that the percutaneous route of apomorphine could be evaluated in humans to test its efficacy in the treatment of motor fluctuations in parkinsonian patients.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryWeakness, easy fatiguing, and lack of endurance are commonly perceived by patients with Parkinson's disease (PD). Although the slowed motor repertoire in PD may underlie these experiences, other abnormalities in skeletal muscle utilization also may be involved. We investigated whether an index of metabolic efficiency during a continuous exercise task, the latency until anaerobic threshold (AT), is altered by L-DOPA (LD). While pedalling a bicycle ergometer against a uniform workload, subjects were monitored for expired O2 and CO2. As compared to an unmedicated state, LD treatment delayed AT by a mean (±SE) of 5.67 ± 0.89 to 6.62 ± 1.23 min (p < 0.05, paired t test). Subjects did not differ in their perceived exertion upon reaching AT. With relief of parkinsonism by LD, the efficiency of energy utilization is also increased in exercised skeletal muscle.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryPainful legs and moving toes is a rare syndrome with controversial physiopathology. We report two cases that were relieved by applying transcutaneous vibratory simulation. The pain relief was objectively evaluated using the nociceptive flexion reflex of the lower limb (RIII reflex). In these patients, we found a deficiency in circulating adenosine levels, which was not found in other chronic painful syndromes (sciatic pain). Based on these observations, we successfully treated patients with painful legs and moving toes by the administration of ATP. The deficit in blood adenosine may be an explanation of the physiopathology of this syndrome.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

SummaryThree patients with hemiballismus received intravenous flumazenil and placebo in a double-blind cross-over study aimed to investigate whether an antagonistic action at the level of the GABA-benzodiazepine receptors may improve choreoballistic movements. No clinical benefit was seen.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID