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Biomedical subjects

D A Bennett

Publications and source records attributed to D A Bennett.

At least 109 records · Page 6Linked to original sources
PubMed1991

Predictors of behavioral disturbance in Alzheimer's disease.

The relationship of behavioral disturbances in Alzheimer's disease to disease severity, age at onset, and the presence of extrapyramidal signs was investigated in three studies. Five categories of behavior disturbance were ascertained through structured interview with the patient's primary caregiver: apathy, agitation, psychotic symptoms, disinhibition, and irritability. In Study 1, measures of disease severity accounted for 42% of the variance in the Apathy scale but less than 20% of the variance in the remaining scales. In Study 2, the presence of extrapyramidal signs was associated with increased Apathy and moderated the association between disease severity and the Psychotic Symptoms and Irritability scales. In Study 3, age at onset was associated with the Agitation scale and moderated the association between disease severity and the Apathy, Psychotic Symptoms, and Irritability scales. The findings are discussed in terms of the clinical heterogeneity within Alzheimer's disease, the possible biological bases of these behavioral disturbances, and the psychometric issues pertinent to their measurement.

Age Factors↗
PubMed1991

Hallucinations and associated factors in Alzheimer's disease.

In a consecutive sample of 230 community-dwelling patients with probable Alzheimer's disease, a structured interview yielded evidence of current hallucinations in 29.1% and misperceptions in another 11.3%. Visual and auditory modalities were similarly represented in apparent hallucinations. Hallucinations prior to the current monitoring period were rare among patients with misperceptions or with no perceptual abnormality. The probability of hallucinations was associated with the severity of cognitive dysfunction, the degree of other behavioral disturbances, and the presence of extrapyramidal signs. A logistic regression model predicting hallucinations based on these diverse clinical features accurately classified 87.0% of the sample.

Activities of Daily Living↗
PubMed1991

Cessation of driving and unsafe motor vehicle operation by dementia patients.

We surveyed 522 consecutive patients from a dementia clinic to assess duration of driving after disease onset and instances of unsafe motor vehicle operation in the preceding 6 months. Among the 333 patients licensed to drive at the onset of dementia, the median duration of driving after onset was 28.6 months. Patients with a clinical diagnosis of Alzheimer's disease drove significantly longer than those with other dementia syndromes. Of the 93 patients still driving at the time of the survey, approximately one third were reported to have had at least one form of unsafe motor vehicle operation in the past 6 months, including 21 patients with motor vehicle accidents. Motor vehicle accidents were associated with use of prescription medications with sedative properties and with lower subjective ratings of the patient's driving ability by the informant.

Accidents, Traffic↗
PubMed1990

Diurnal blood pressure in patients with mild-to-moderate hypertension treated with once-daily benazepril hydrochloride.

This study evaluated the blood pressure effects of administration of once daily oral benazepril hydrochloride, a new angiotensin-converting enzyme (ACE) inhibitor, for mild-to-moderate hypertension. After a 2 to 4 week placebo baseline period, patients with diastolic blood pressure between 95 and 114 mm Hg, were randomized to receive either placebo or benazepril hydrochloride, 5, 10, 20, or 40 mg, once daily in double-blind fashion for 28 days. Blood pressure was measured predose and at 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after the dose during inpatient observation days at the end of the placebo baseline period, and on the first and last day of the double-blind treatment period; and 24 hours after the dose at weekly outpatient visits. All doses of benazepril hydrochloride resulted in clinically important reductions in diastolic and systolic blood pressures that lasted between 12 and 24 hours after both the first dose, and following the last dose after 4 weeks of treatment. The findings indicate that benazepril hydrochloride may be clinically useful as once-daily monotherapy in many patients with hypertension.

Administration, Oral↗
PubMed1990

Clinical diagnosis of Binswanger's disease.

To aid in the prospective study of Binswanger's disease, a poorly understood form of vascular dementia, a standardised criteria for its antemortem diagnosis was proposed. These criteria include dementia, bilateral radiological abnormalities on computed tomography (CT) or magnetic resonance imaging (MRI), and at least two of the following three clinical findings: A) a vascular risk factor or evidence of systemic vascular disease; B) evidence of focal cerebrovascular disease; and C) evidence of "subcortical" cerebral dysfunction. These criteria were validated in two ways. First, by retrospectively applying them to a series of 30 demented patients with various pathological diagnoses. Second, by prospectively applying them to a series of 184 patients with clinically typical Alzheimer's disease. The sensitivity and specificity of the criteria appear adequate for use in clinical research.

Alzheimer Disease↗
PubMed1990

CGS 19755: a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist with anticonvulsant, anxiolytic and anti-ischemic properties.

CGS 19755 is a potent and selective competitive antagonist at NMDA receptors in the brain. In preclinical animal tests, the compound produces anticonvulsant, anxiolytic and anti-ischemic effects. CGS 19755 is not very active when administered orally, and intravenous administration is the most practical for clinical application. The anti-ischemic potential of CGS 19755 provides the most attractive application for clinical investigation.

Animals↗
PubMed1989

Behavioral pharmacological profile of CGS 19755, a competitive antagonist at N-methyl-D-aspartate receptors.

CGS 19755 (cis-4-phosphonomethyl-2-piperidine-carboxylic acid), a competitive antagonist at N-methyl-D-aspartate (NMDA)-preferring receptors, blocked both NMDA-induced convulsions in normal CF1 mice and sound-induced wild running in seizure-prone DBA/2 mice. The ED50 values for CGS 19755 to produce these effects (in the range of 2 mg/kg i.p.) were at least 3-fold lower than those which impaired the traction reflex, an index of motor coordination. When administered p.o. by gavage, CGS 19755 had little or no effect in these test procedures. In an experimental model of anxiety in rats, CGS 19755 significantly increased conflict responding within a relatively narrow dose range (minimum effective dose, 1.73 mg/kg i.p.). At higher doses of CGS 19755, this effect appeared to be obscured by drug-induced reductions in overall responding. Potential muscle relaxant effects were also suggested by the generalization of CGS 19755 to diazepam discriminative stimuli (ED50 = 9.0 mg/kg i.p.) and by impaired rotorod performance (ED50 = 6.2 mg/kg i.p.) in rats. Although some resemblances were apparent between the behavioral effects of CGS 19755 and those of phencyclidine-type drugs, the phencyclidine-like behaviors appeared only at considerably higher doses of CGS 19755 than those associated with anticonflict activity, and only partial generalization of CGS 19755 to dexoxadrol was observed at high doses. CGS 19755 promises to be an important new research tool for investigating the function of brain NMDA receptors.

Animals↗
PubMed1989

CGS 20625, a novel pyrazolopyridine anxiolytic.

CGS 20625 (2-(4-methoxyphenyl)2,3,5,6,7,8,9,10-octa hydrocyclohepta[b]pyrazolo-[3,4-d]pyridin-3-one) is a potent and selective ligand for the central benzodiazepine receptor (IC50 = 1.3 nM), with little or no affinity to several other neurotransmitter receptor binding sites in vitro. CGS 20625 had a gamma-aminobutyric acid ratio of 0.9 and increased t-[35S]butylbicyclophosphorothionate binding by 20% in vitro, a profile indicative of a partial agonist or mixed agonist/antagonist. In vivo, CGS 20625 blocked a pentylenetetrazol discriminative cue with an ED50 = 1.7 mg/kg p.o. The compound selectively increased conflict responding in the Cook-Davidson paradigm with a minimal effective dose of 0.3 mg/kg p.o., as compared with 3.0 mg/kg p.o. for diazepam. At doses as high as 100 mg/kg p.o., CGS 20625 had no effect on variable interval responding, suggesting minimal sedation. Unlike diazepam, CGS 20625 had no effect on rotorod performance at doses up to 100 mg/kg p.o. indicating no overt muscle relaxation, and did not potentiate the action of ethanol in this behavioral paradigm. Also, CGS 20625 had no marked effect on locomotor behavior, did not potentiate hexobarbital sleep time and had no sedative activity at doses up to 300 mg/kg p.o. CGS 20625 was efficacious in preventing pentylenetetrazol-induced seizures (ED50 = 0.7 mg/kg p.o.), had less efficacy with no clear dose-response relationship against picrotoxin-induced seizures and had no effect on either strychnine or electroshock-induced convulsions at doses up to 300 mg/kg p.o.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Comparison of discriminative stimuli produced by full and partial benzodiazepine agonists: pharmacological specificity.

Benzodiazepines produce discriminative stimuli that are stereospecific and antagonized by specific benzodiazepine receptor antagonists. The potency of these stimuli correlate with the ability of these compounds to bind to the benzodiazepine receptor complex. These data indicate that benzodiazepine stimuli are transduced via the benzodiazepine receptor. The underlying basis of these stimuli is unclear. Results with novel compounds that produce preclinical anxiolytic effects without the sedation and muscle relaxation of the classical benzodiazepines suggest that muscle relaxation may contribute to these stimuli. A direct comparison of discriminative stimuli established on a classical benzodiazepine agonist with the stimuli established on a partial benzodiazepine agonist supports the possibility that the classical benzodiazepine cue is mediated by a muscle relaxant effect, while the partial agonist cue is related to the anxioselectivity of the compound.

Animals↗
PubMed1988

A comparison of PCP-like compounds for NMDA antagonism in two in vivo models.

The PCP-like compounds ketamine and dexoxadrol were evaluated in two behavioral test procedures known to be sensitive to competitive N-methyl-D-aspartate (NMDA) receptor antagonists. In the NMDA-induced convulsion test in mice, ketamine and dexoxadrol blocked convulsant activity only at doses that also induced nonspecific effects of PCP-like behaviors, thereby confounding the interpretation of results. These compounds also blocked NMDA-induced discriminative stimuli in rats; however, this effect was produced at doses lower than those which induced the nonspecific behavioral effects. These results provide evidence that in behavioral procedures, PCP-like compounds may block excitatory amino acid receptor stimulation by NMDA. The NMDA discrimination identifies these interactions without the influence of motor deficit or other behavioral motor effects.

Animals↗
PubMed1987

N-methyl-D-aspartate produces discriminative stimuli in rats.

Male Sprague Dawley rats were trained to discriminate an interoceptive effect associated with a subconvulsant dose (30 mg/kg i.p.) of the excitatory amino acid receptor agonist, N-methyl-D-aspartate (NMDA). Approximately 60% of the rats learned to discriminate this compound from saline in 45 +/- 5 sessions, and the stimuli were dose dependent (ED50 value = 13.6 mg/kg i.p.). The specific NMDA receptor antagonist, 3-[+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), blocked NMDA-induced discriminative stimuli with an ED50 value equal to 2 mg/kg i.p., confirming that the NMDA cue is mediated by activation of NMDA receptors. Through the use of NMDA discriminative stimuli, the consequences of NMDA excitation can be studied in vivo and compounds with potential NMDA antagonist properties can be identified.

Animals↗