摘要:

Summary: The carrier molecule that transports dopamine (DA) across the synaptic membrane is known as the dopamine transporter (DAT). Depending on the ionic conditions, DAT may function as a mediator of both the inward directed DA transport known as the “reuptake” and the outward directed DA transport known as the “release.” The functional significance of DAT is in the regulation of DA neurotransmission by terminating the action of DA in the synapse via reuptake. With use of DAT binding as a presynaptic marker to measure altered DA innervation, abnormalities of the DAT binding have been demonstrated in idiopathic Parkinson's disease, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity, and progressive supranuclear palsy. Moreover, the identification of DAT as the neuronal element that mediates the addictive properties of cocaine highlights its significance in cocaine addiction. Cocaine binding in the brain is heterogeneous, and there is an uneven distribution of the high- and low-affinity binding sites across the anatomical regions. Regional differences in ligand binding are observed by using both [3H]cocaine and the diphenyl-substituted piperazine derivatives known as the “GBR series” of ligands. The identification of compounds that inhibit the binding of cocaine without affecting DA uptake could potentially lead to development of medications for cocaine abuse. Furthermore, clarification of the various binding domains that may be relevant to transporter function in human neuropsychiatric disorders may lead to the development of new medications for schizophrenia, Tourette's disease, and drug addiction.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary: Ticlopidine hydrochloride, an inhibitor of platelet aggregation that has been approved for use in the United States for secondary stroke prevention, may be more effective than aspirin for the secondary prevention of stroke, but this advantage decreases greatly over time. The pharmacology, adverse effects, efficacy, drug interactions, and indications for ticlopidine are discussed here with summaries of various clinical trials. The drug is more costly than aspirin, and patients must have complete blood counts during the first 3 months of therapy. It is recommended for those who cannot take aspirin and may be more effective in certain groups—nonwhites, diabetics, and women and those with vertebrobasilar ischemia, intermittent claudication, unstable angina, and nonproliferative retinopathy.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary: Although the current trend is to use monotherapy in the treatment of epilepsy, combination therapy is still employed in patients who have failed to respond to monotherapy. There is little clinical or experimental documentation of evidence against or in favor of anticonvulsant combination therapy. In this context, anticonvulsant and neurotoxic pharmacodynamic interactions between phenytoin (PHT) and valproate (VPA) were assessed in an experimental model in mice. All results were expressed in terms of brain drug concentrations for eliminating any pharmacokinetic interaction from the analysis. Both the median neurotoxic and the median anticonvulsant brain concentrations were determined for each drug used alone and for the combination. The interaction for the combination of PHT and VPA was shown to be supraadditive for the anticonvulsant activity, indicating an antiepileptic potentiation, whereas neurotoxicity was simply additive. These results suggest a potential benefit in terms of overall efficacy versus toxicity for the combination of PHT and VPA, as compared with PHT or VPA used alone.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary: After overnight drug withdrawal and in the fasting state, 11 patients with Parkinson's disease (PD) and a fluctuating response to chronic levodopa treatment were given, in random sequence on consecutive days, equivalent levodopa doses (with peripheral decarboxylase inhibitor) (a) as levodopa methyl ester (ME), (b) as Sinemet CR, or (c) as half the dose of ME together with a halved tablet of Sinemet CR. All patients turned ON rapidly after treatments a and c, but only half did so after treatment b. On period duration was longest after treatment c, intermediate after treatment a, and shortest after treatment b. Pharmacokinetic analysis in a subset of 6 patients revealed no significant difference between treatments a and c, although there was a trend for t1/2 to be longer after treatment c. We conclude that giving ME with a halved tablet of Sinemet CR provided a useful clinical balance between rapid onset and extended duration of action of at least the first levodopa intake of the day. In view of differing release profiles between whole and halved tablets of Sinemet CR, similar single-dose pharmacokinetic studies, followed by sequential-dose clinical studies, are indicated when Sinemet CR 125 tablets soon become available.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary: In this study, we measured the relationship between plasma and cerebrospinal fluid (CSF) apomorphine levels and their clinical effects in two patients with Parkinson's disease (PD). After subcutaneous injection of apomorphine, serial samples of plasma and lumbal CSF were taken and serial scoring of motor responses was done using the Webster Rating Scale. The ratio of the highest level of apomorphine in CSF and plasma was 0.036 for patient A and 0.025 for patient B. The time lag between the highest level of apomorphine in plasma and CSF was 20 min for patient A and 10 min for patient B. Plasma levels of apomorphine correlated weakly with clinical motor responses. However, we could establish a highly strong correlation between apomorphine CSF levels and clinical motor responses: 0.93 and 0.89 for patients A and B, respectively. We conclude that a two-compartment pharmacokinetic model explains the clinical effects of apomorphine better than does a one-compartment model. In a two-compartment model, clinical effect can clearly be correlated to apomorphine levels in the central compartment.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary: The utility of L-tyrosine (10 g/day in four divided doses) as an adjuvant to molindone (150 mg/day) in the treatment of schizophrenia was investigated using a placebo-controlled, double-blind crossover design (3 weeks on L-tyrosine, 3 weeks on placebo). The objective of this inpatient study was to increase dopaminergic neural transmission along mesocortical projections in patients by increasing the precursor availability of L-tyrosine for dopamine biosynthesis. Theoretically, this approach might lessen both negative and positive symptoms of schizophrenia and improve frontal lobe-mediated neuropsychological performance. There was no evidence of statistically significant improvement conferred by L-tyrosine as measured by weekly Brief Psychiatric Rating Scale (BPRS), Schedule for the Assessment of Negative Symptoms (SANS), or Clinical Global Impressions (CGI) scales. The 12-h trough plasma level of L-tyrosine was significantly higher in all patients during the L-tyrosine phase of the study (t = −3.9, df = 20, p = 0.0009). At the end of each 3-week study period, no significant differences could be found in Wisconsin Card Sorting Test (WCST) or memory test performance. Smooth-pursuit eye movement (SPEM) performance had significantly more saccadic intrusions during the L-tyrosine supplementation phase compared to the placebo period. This increase in saccades during SPEM suggests that the tyrosine supplementation might have had some central effect.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary: Immunodeficiency is frequently invoked as an ethiopathogenetic factor for many somatic diseases. On the other hand, stress, depression, and psychotic disturbances are associated with severe immunological disorders. Taking into account that the benzodiazepines (BZ) are the psychoactive drugs more widely used than any other to treat psychological disturbances, it seems important to elucidate the immuno-enhancing or immunosuppressant potential of such drugs. Our goal was easily reached, since 69% of the outpatients visiting our Institute are chronic BZ consumers and because neurochemical, hormonal, immunological, and psychiatric investigations are routinely performed on all of our patients. In the present study, immune function was investigated on two occasions: while the patient was on active medication and 15 days after discontinuation. We concluded that chronic consumption of BZ provokes significant immunological disorders that should be further investigated. Said disorders could not be linked to a pre-existing affective disease or psychosis, since we only selected those BZ users in whom psychiatric investigations ruled out a past or present history of major psychiatric disease.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary: We made a double-blind, crossover comparison of buspirone (10 mg orally, twice a day) and placebo in 10 patients with Parkinson's disease and levodopa-induced dyskinesias. The duration of the study was 3 weeks, for both buspirone and for placebo treatment. Chronic therapies remained unchanged. The extrapyramidal symptoms, dyskinesias, and anxious/depressive symptoms were evaluated at the beginning of the study and after the buspirone and placebo treatments. Seven patients concluded the trial. The extrapyramidal symptoms, evaluated in both the “off” and “on” states during an oral L-Dopa test, did not show any worsening during the trial. Buspirone significantly lessened the severity of levodopa-induced dyskinesias in five of the seven patients, whereas it proved ineffective in the two patients with the mildest dyskinesias. There were no changes in the mild anxious and depressive symptoms at any time during the study. The activities of buspirone on the serotonin and dopamine systems might have led to the antidyskinetic effect we observed. At daily dosages of 20 mg, buspirone might prove effective in reducing levodopa-induced dyskinesias without worsening of parkinsonism.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary: We investigated the possible relationship between schizophrenia, neuroleptic treatment, and platelet monoamine oxidase (MAO) activity. Platelet MAO activity was similar in neuroleptic-naive schizophrenic patients and healthy controls and was not affected by chronic (10-week) perphenazine treatment. A relationship between platelet MAO activity and central disturbances in schizophrenia remains uncertain.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Summary: The present study compares lacrimal secretion in control subjects and patients with Parkinson's disease with use of Schirmer's test. Tear secretion was decreased in Parkinson's disease. The reduction was more marked in stages III-IV than in stages I-II. The results are discussed in relationship with autonomic dysfunction in Parkinson's disease.

ISSN:0362-5664    

出版商:OVID    

年代:1994

数据来源: OVID