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Biomedical subjects

J D Roache

Publications and source records attributed to J D Roache.

At least 37 records · Page 2Linked to original sources
PubMed1993

Intravenous flumazenil following acute and repeated exposure to lorazepam in healthy volunteers: antagonism and precipitated withdrawal.

The effects of i.v. administered flumazenil (3.0 mg) were studied in healthy male subjects who received pretreatment with p.o. placebo or lorazepam. The duration of placebo or lorazepam (3.0 mg single p.o. daily dose) pretreatment before a flumazenil or placebo injection was 1, 3, 7 or 14 days in four sequential groups of subjects. Initial administration of lorazepam produced a classic sedative profile of effects on various psychomotor/behavioral performance, observer-rated and subject-rated measures. Tolerance to repeated daily administration of lorazepam was suggested by a progressive diminution of performance disrupting effects. In subjects pretreated with placebo, flumazenil increased subject-ratings of dizziness over preinjection ratings. Flumazenil produced an immediate reversal of lorazepam effects in subjects who were not tolerant to lorazepam (1- and 3-day pretreatment groups). Flumazenil did not precipitate withdrawal symptoms in subjects who received a single administration of lorazepam. Precipitated withdrawal symptoms were evident after 3 and 7 days of lorazepam pretreatment, and there was a tendency toward precipitated withdrawal symptoms (that included one panic attack) after 14 days of lorazepam pretreatment. Precipitated withdrawal was characterized by an elevation in subject-rated symptoms including dizziness, tenseness, tachycardia, perceptual disturbance and sweating. Symptoms were maximal immediately after injection, usually mild in severity and usually resolved within 1 hr. There was no evidence of precipitated withdrawal on psychomotor/behavioral performance or observer ratings. The present study provides the strongest human experimental evidence to date that flumazenil can precipitate withdrawal symptoms after a history of repeated benzodiazepine exposure.

Adolescent↗
PubMed1991

Effects of triazolam on human aggressive, escape and point-maintained responding.

Placebo and triazolam (0.125, 0.25 and 0.5 mg/70 kg of body weight) were administered to male subjects under double-blind conditions prior to experimental sessions which provided three operant response options. These options were: 1) responding maintained by the presentation of points exchangeable for money, 2) responding which ostensibly resulted in the subtraction of points from a fictitious person was termed aggressive since this responding resulted in the delivery of an aversive stimulus to another person, and 3) responding which ostensibly protected the subject's point counter from subtractions initiated by the other person and was termed escape. Aggressive and escape responding were initiated by subtracting points from the subject. Point subtractions were attributed to the other person. Aggressive and escape responding were maintained by initiation of provocation-free intervals (PFI), during which no further point subtractions were presented. Triazolam produced dose-dependent decreases in point-maintained and escape responding. The effects of triazolam on aggressive responding varied across subjects.

Adult↗
PubMed1991

Performance and physiological measures in abuse liability evaluation.

Abuse liability testing involves an evaluation of the likelihood of drug self-use and also an evaluation of the harmful effects of drug use. This paper reviews the rationale and utility of examining performance and physiological measures in clinical abuse liability evaluation. It is concluded that there are three important reasons to employ such measures in abuse liability studies: (1) to serve as a reference point to allow for between drug and across measure comparisons; (2) to directly quantify dose-response functions on multiple dimensions of drug effect and thus evaluate the overall profile of effects; and (3) to provide information on the likelihood that drug use will produce harmful effects. The review illustrates each of these purposes and briefly summarizes conclusions from previous studies employing performance and physiological measures in the abuse liability evaluation of sedatives, stimulants, and opioids.

Affect↗
PubMed1990

Benzodiazepine-induced impairment of matching-to-sample performance in humans.

The effects of benzodiazepines on a visual pattern matching-to-sample (MTS) task were examined in nine healthy male volunteers. The MTS task employed randomly generated checkerboard-like stimuli presented on a video display. The sample and two comparison stimuli were simultaneously presented. Nonmatching comparison stimuli were randomly generated to be 3.125, 6.25, 12.5, 25.0, 37.5, or 50.0 percent different from the sample. Subjects responded on left or right button manipulanda to identify the matching comparison stimulus. The nonmatching stimulus condition was maintained constant for a 60-sec component and the percentage difference of the nonmatching stimuli was systematically varied across multiple components. The effects of triazolam (2.25-9.0 micrograms/kg) and lorazepam (7.5-45 micrograms/kg) were examined in a within-subjects, double-blind, placebo-controlled study. Under placebo conditions, response rates and accuracy were a positive function of the nonmatching stimulus discriminability. Triazolam produced dose-related decreases in response rate at nonmatching stimulus conditions greater than or equal to 25%. Only the 9.0 micrograms/kg dose of triazolam decreased accuracy and this occurred across all nonmatching stimulus conditions. Lorazepam effects were qualitatively similar but less robust than those of triazolam.

Adult↗
PubMed1990

The effects of codeine on human aggressive responding.

Ten healthy male research subjects received placebo, 25, 50 and 75 mg/70 kg of codeine in a controlled laboratory setting. During each session subjects had two response options. The non-aggressive response option was maintained by points exchangeable for ten cents. The aggressive response option ostensibly subtracted a point from the subject's fictitious partner. Aggressive responding was engendered by point subtractions attributed to a fictitious partner. Codeine did not significantly alter the frequency of monetarily reinforced, nonaggressive, responding. Aggressive responding was significantly increased at the 50 mg/70 kg dose of codeine. The frequency of aggressive responses during the placebo sessions preceding administration of the first codeine dose were significantly and positively correlated with scores on the Buss-Durkee Hostility Scale. Aggressive responding increased for four of five subjects scoring below the median on the Buss-Durkee Hostility Scale at the 50 mg/70 kg dose; while administration of 50 mg/70 kg increased aggressive responding of one subject who scored above the median. Aggressive responding for both groups of subjects was unaffected by the 75 mg/70 kg dose.

Administration, Oral↗
PubMed1990

Addiction potential of benzodiazepines and non-benzodiazepine anxiolytics.

This paper reviews the addiction potential of all benzodiazepines currently available in the U.S.A. as well as several non-benzodiazepine anxiolytic drugs. Addiction potential was assessed by separately considering the potential for these drugs to produce three different phenomena of addiction; namely, physical dependence, psychological dependence and deleterious consequences. This review focuses on human studies conducted with research volunteers outside the therapeutic context and also on clinical studies conducted with patients receiving treatment in the therapeutic context. It is concluded that benzodiazepines have a reduced addiction potential in comparison to the predecessor barbiturates. Conclusions regarding the relative addiction potential of several non-benzodiazepine anxiolytics are difficult due to a paucity of data; however limited evidence suggests a reduced addiction potential for several of these compounds. Within the benzodiazepine class, qualitative differences in addiction potential between individual drugs are not well established.

Anti-Anxiety Agents↗
PubMed1990

Dose-response evaluation of the amnestic effects of triazolam and pentobarbital in normal subjects.

The effects of placebo, triazolam (0.25, 0.5, and 0.75 mg), and pentobarbital (100, 200, and 300 mg) were examined in seven normal male volunteers using a double-blind, Latin Square, balanced crossover design. Before and at hourly intervals after oral drug administration at approximately 10 a.m., subjects completed subject ratings of drug effects, psychomotor performance tasks, and two versions of a number recall task in which eight-digit number stimuli were recalled by reproduction on a numeric keypad. In one version, number stimuli were displayed on a video screen for varying lengths of time (3, 6, or 9 seconds) before immediate recall. In another version, subjects initially reproduced a continuously displayed number and then recalled the number following an immediate or a 16-second delay interval. Both triazolam and pentobarbital produced dose-related effects on all measures. Relative potency comparisons showed that triazolam was 270-384 times more potent than pentobarbital on subject ratings and psychomotor measures but was 406-647 times more potent than pentobarbital on measures of recall impairment. Recall performance deficits produced by both triazolam and pentobarbital at short (3-second) stimulus presentation times were attenuated at longer presentation times. With the variable delay task, triazolam but not pentobarbital interacted with the delay interval and produced impairments only at the 16-second delay condition. These data indicate that both triazolam and pentobarbital quantitatively impair acquisitional processes involved in short-term recall performance. Furthermore, triazolam may have a greater potential than pentobarbital to produce memory impairment, as reflected by its greater relative potency on these measures and its tendency to interfere with retention over short delay intervals.

Adult↗
PubMed1989

Diazepam and triazolam self-administration in sedative abusers: concordance of subject ratings, performance and drug self-administration.

The reinforcing effects of diazepam (DZ), triazolam (TZ) and placebo were examined in eight male subjects with histories of sedative abuse. DZ (40 or 80 mg), TZ (1.0 or 2.0 mg) and placebo were each individually available for oral self-administration using a double-blind within-subject design. After an initial sampling exposure, subjects could self-administer a single dose of drug on each of 6 days by completing a progressively increasing bicycle riding requirement. All subjects initially self-administered DZ and TZ but a decreasing number of subjects continued to self-administer drugs on the remaining days; there was no difference between DZ and TZ in the total number of self-administrations. Placebo was self-administered only by one subject on two occasions. Performance measures showed that TZ produced greater memory impairment than DZ and that DZ produced residual psychomotor impairment on the next day. With repeated dosing, evidence of tolerance was seen for both drugs on psychomotor and memory performance and subject ratings of drug liking. A few modest correlations of drug self-administration and subject-ratings were obtained, suggesting some correspondence of subject verbal and drug self-administration behaviors, but these measures did not covary in a completely consistent manner.

Adult↗
PubMed1987

Interactions of diazepam and caffeine: behavioral and subjective dose effects in humans.

The effects of diazepam (DZ) (0, 10, and 20 mg) and caffeine (CAF) (0, 200, 400, and 600 mg) alone and in combination were examined in nine healthy male subjects using a within-subject experimental design in which all subjects received all twelve possible dose combinations. Drug effects were assessed using various psychomotor and cognitive performance tasks, staff (observer) ratings of subject behavior, and subject ratings of mood and drug effect. DZ treatment alone impaired performance on all tasks and produced staff and subject ratings indicative of sedative drug effects. CAF treatment alone facilitated performance on two psychomotor tasks requiring rapid reaction speed and increased staff ratings of subject restlessness and subject ratings of tension, alertness, arousal, and CAF symptoms. CAF generally antagonized the DZ-induced ratings of sedation and impairment of psychomotor performance; however, CAF did not consistently antagonize the DZ impairment of immediate recall or delayed recognition memory performance. DZ antagonized the CAF-induced staff-rated restlessness, and subject-ratings of tension, alertness, arousal and CAF symptoms. The results generally support the hypothesis that DZ and CAF produce antagonistic effects through functionally opposing mechanisms, however, the observed effects of drug combinations are dependent on the specific doses being tested and on the measures of drug effect being examined.

Adolescent↗