摘要:

Parkinson's disease (PD) is frequently associated with psychiatric problems. Depression generally responds to antidepressant medications or to electroconvulsive therapy (ECT). The nondepressive psychoses generally require a reduction in parkinsonian medications, or possibly a “drug holiday.” In patients whose psychosis fails to respond to a reduction in medication or who cannot tolerate the worsening parkinsonism, an antipsychotic drug should be added. Clozapine is probably the drug of choice, with low potency neuroleptics being second-line options.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Neurogenic orthostatic hypotension is an incapacitating symptom of central and peripheral autonomic nervous system degeneration. It occurs in such clinical conditions as multiple system atrophy, pure autonomic failure, and small-fiber peripheral neuropathies. Although many treatments are available, their effects are inconsistent, unsustained, and complicated by side effects. 3,4-Dihydroxyphenylserine is a synthetic, unnatural amino acid that is an immediate norepinephrine precursor. There is theoretical and clinical evidence supporting the use of this agent in the treatment of neurogenic orthostatic hypotension in patients with peripheral and central autonomic nervous system dysfunction. We review the biochemistry, pharmacokinetics, and possible mechanisms of action and clinical utility of this agent in the treatment of neurogenic orthostatic hypotension.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The gastrointestinal transit and systemic absorption of Sinemet CR (50–200) controlled-release tablets and standard Sinemet (25–100) immediate-release (IR) tablets have been studied in fasted and fed healthy human subjects. Both formulations were labelled with a gamma-emitting radionuclide and their gastric emptying, colon arrival and in vivo disintegration profiles monitored using gamma scintigraphy. The IR dosage forms were found to disperse soon after administration and to empty rapidly from both fasted and fed stomachs. Erosion of the CR system was independent of food or stomach pH. The CR tablet was observed to disintegrate fully in the gastrointestinal (GI) tract, resulting in complete release of levodopa over a 3–4 h time period. Considerable intersubject variation was found to exist for levodopa absorption. Absorption was more protracted with Sinemet CR than with standard Sinemet, due to the controlled release characteristics of the tablet matrix. There was no rapid initial absorption phase and instead, a gradual build-up in the absorption profile occurred.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Ninety-four patients with early Parkinson's disease were investigated in a double-blind, placebo-controlled evaluation of MK-458 [hydroxypropyl methylcellulose/lactose matrix (HPMC)], a sustained release formulation of a novel naphthoxazine compound with selective D-2 dopamine receptor agonism. Patients were previously untreated with dopaminergic drugs. Efficacy was assessed by clinical rating scales and by patient self-evaluation. MK-458 (HPMC) caused a significant decrease in most parkinsonian symptoms. Though disability rating scores were lowered by the drug, the scores did not differ significantly from placebo. However, statistically significant improvement occurred with MK-458 (HPMC) on both the physician and the patient global assessments. Adverse reactions such as nausea and vomiting, sedation, confusion, and hallucinations occurred more with MK-458 (HPMC) than with placebo. MK-458 (HPMC) possesses antiparkinsonian efficacy in early Parkinson's disease; however, side-effects are frequently associated with its use. Selective D-2 receptor agonists, such as MK-458 (HPMC). may not be the ideal treatment as monotherapy for Parkinson's disease.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We studied the effectiveness of OR-611 and OR-462. two novel inhibitors of the enzyme catechol-O-methyltransferase (COMT), on 3-O-methyldopa (OMD) formation in cynomolgus monkeys following intravenous levodopa administration? OR-611 dosc-dependently reduced the area under the OMD concentration-vs-time curve, reduced maximum plasma OMD concentrations, delayed the time to peak OMD levels, reduced systemic levodopa clearance, and prolonged the elimination half-life of levodopa. Similar effects on peripheral levodopa metabolism were seen with doses of 15 mg/kg of OR-611 and OR-462, its sister compound, which lacks the ability to penetrate the central nervous system (CNS).

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The hemodynamic and biochemical effects of cabergoline, a new ergoline derivative with selective, potent, and long-lasting dopamine (DA) agonistic properties, were evaluated in 19 parkinsonian patients, all previously identified as stable responders to levodopa plus L-Dopa decarboxylase inhibitor. The purpose of the study was to find markers capable of predicting the development of cardiopressor side effects during DA-agonistic therapy. Blood pressure (BP), heart rate, and plasma catecholamine responses to a standard meal and a tilt table test were evaluated before and during cabergoline therapy. Cabergoline (1.0 mg/day x os) in this open study significantly reduced the BP response to standing exclusively in the subgroup of patients who exhibited marked postprandial hypotension rnbaseline conditions. The patients subsequently experienced a partial recovery at day 7 of treatment. This finding indicates that postprandial hypotension is an early marker of autonomic failure in patients with Parkinson's disease (PD) and suggests the usefulness of evaluating cardiopressor response to a standard meal before starting new DA-agonist therapy in PD.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

This study investigated alterations in the disposition and pharmacody namics of methamphetamine HCI after daily administration. Six male paid volunteers familiar with the use of amphetamines participated. Each subject was administered 10 mg of methamphetamine HCI as a slow-release preparation (Desoxyn Gradumets) at 9 a.m. for 13 consecutive days (days 2–14 of the study). On days 1 and 15 the subjects were challenged with 10 mg of oral deuterated methamphetamine HCl. Deuterated drug was used to differentiate plasma concentrations of challenge doses from those of daily doses. The heart rate, subjective perception of “high,” and plasma concentrations of methamphetamine were examined on days I and 15. Repeated ANOVA measures indicate that a significant decrease in heart-rate acceleration in response to methamphetamine challenge occurred on day 15 (F(1,5) = 8.26, p ± 0.035]. However, no significant change in either the subjective ratings of “high” or the plasma concentrations of deuterated methamphetamine occurred. These findings indicate that the disposition of methamphetamine and its subjective effects were not altered by this period of daily exposure to a low dose of the drug. In contrast, tolerance to the heart-rate accelerating effect was observed.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The purported α2-adrenergic agonist clonidine was found to inhibit rest tremor at doses of 0.023–0.1 mg/kg in the 1-methyl-4-phenyl-1.2.3,6-tetrahydropyridine monkey model of parkinsonism. The effect was dose dependent, but sedation and reduced mobility were observed. Atropine at doses of 0.1–1 mg/kg also reduced tremor in a dose-dependent fashion, but side-effects in the form of agitation, dilated pupils, and dry mouth were seen. When the two drugs were combined, however, we saw a significant potentiation of the antitremor effect. We could even abolish tremor with doses of atropine and clonidine that by themselves were without effect. The side-effects were almost eliminated by the combination.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A 19-year-old girl with a long-standing history of kyphoscoliosis misdiagnosed as idiopathic was offered corrective surgery on several occasions but fortunately refused, since neurological examination later found evidence of mild dystonic posturing in the neck and right leg. Symptoms worsened toward evening but improved with rest. Treatment with low doses of levodopa led to total remission within a month. Our case illustrates that dopa-responsive dystonia can manifest spinal curvature as the major symptom and warrants its inclusion in the differential diagnoses of idiopathic kyphoscoliosis.

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1991

数据来源: OVID