Impaired performance on delayed matching in monkeys by heptabarbitone, pentobarbitone sodium and quinalbarbitone sodium

Nicholson, Anthony N.; Wright, Catherine; Ferres, Helen M.

doi:10.1016/0028-3908(73)90090-7

Cited by 22 publications

(12 citation statements)

References 3 publications

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“…This would suggest that pentobarbitone sodium and flurazepam hydrochloride modified central nervous and neuromuscular delays, but that nitrazepam may have had a more complicated effect. Other studies in man (Malpas et al, 1970;Bond & Lader, 1972) have suggested that nitrazepam leads to greater disturbances in behaviour than barbiturates, and these observations have been supported by studies in the monkey on delayed matching behaviour (Nicholson, Wright & Ferres, 1973;Nicholson & Wright, 1974).…”

Section: Discussionmentioning

confidence: 74%

Comparison of the residual effects of two benzodiazepines (nitrazepam and flurazepam hydrochloride) and pentobarbitone sodium on human performance.

Borland¹,

Nicholson²

1975

Brit J Clinical Pharma

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1 The residual effects of two benzodiazepines, nitrazepam (10 mg) and flurazepam hydrochloride (30 mg), and pentobarbitone sodium (200 mg) were studied by adaptive tracking and by reaction time. Performance was measured at 10 h, 13 h, 16 h, 19 h and 34 h after ingestion of each drug. Impaired performance on adaptive tracking was observed at 10 h, 13 h, 16 h and 19 h after nitrazepam and pentobarbitone sodium and at 10 h, 13 h and 16 h after flurazepam hydrochloride. Enhanced performance was observed at 34 h after nitrazepam and pentobarbitone sodium. 2 Increased reaction time persisted to 16 h after nitrazepam, flurazepam hydrochloride and pentobarbitone sodium and reaction time was also increased at 34 h after nitrazepam and pentobarbitone sodium. 3 During the morning immediately after ingestion, the subjects as a group were able to differentiate correctly between placebo and drugs, but they were not able to assess accurately the persistence of the residual effects of nitrazepam and pentobarbitone sodium. 4 Flurazepam hydrochloride would appear to be a more promising benzodiazepine than nitrazepam for use as a hypnotic by persons involved in skilled activity. There was a rapid recovery of performance during the afternoon and, unlike pentobarbitone sodium and nitrazepam, subjects retained the ability to recognize impaired skill.

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Section: Discussionmentioning

confidence: 74%

Comparison of the residual effects of two benzodiazepines (nitrazepam and flurazepam hydrochloride) and pentobarbitone sodium on human performance.

Borland¹,

Nicholson²

1975

Brit J Clinical Pharma

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“…The task (Konorski, 1959;Roberts & Bradley, 1967;Nicholson et al, 1973) required the animal to differentiate between two stimuli separated by a 4 s delay. The animal was required to press a lever during the presentation of the second stimulus if the stimuli were like (GO response), and to refrain from pressing the lever if the stimuli were unlike (NO-GO response).…”

Section: Methodsmentioning

confidence: 99%

“…With barbiturates and benzodiazepines behaviour is impaired (Nicholson, Wright & Ferres, 1973;Nicholson & Wright, 1974) but the effect of benzodiazepines would appear to be more complex than that of the barbiturates. Unlike the barbiturates, impaired differentiation with benzodiazepines may be related to the nature of the response demanded (GO or NO-GO), and this would suggest that inhibitory and disinhibitory behaviour may be involved.…”

Section: Introductionmentioning

confidence: 99%

BEHAVIOURAL AND PHARMACOKINETIC STUDIES IN THE MONKEY (Macaca mulatta) WITH DIAZEPAM, NORDIAZEPAM AND RELATED 1,4‐BENZODIAZEPINES

Curry

Whelpton

Nicholson

et al. 1977

British J Pharmacology

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1Behavioural activity (delayed differentiation and spatial delayed alternation) and pharmacokinetics of diazepam and its metabolites, N-desmethyldiazepam (nordiazepam), 3-hydroxydiazepam (temazepam) and 3-hydroxy-N-desmethyldiazepam (oxazepam), and of dipotassium clorazepate (clorazepate), were studied in the monkey (Macaca mulatta). Diazepam and its metabolites (1.8 and 3.0 mg/kg) and clorazepate (2.6 and 4.3 mg/kg) were given by intraperitoneal injection. 2 Hydroxylation of diazepam (temazepam and oxazepam) led to a loss of, or a considerable reduction in, behavioural activity, whereas activity was preserved, though modified, by demethylation (nordiazepam). It was not possible to establish change in behaviour at specific time intervals after clorazepate, but combined performance data revealed an effect. 3 The maximum mean plasma concentrations of diazepam, temazepam, oxazepam and clorazepate were observed at 0.5 h, and the maximum mean plasma concentration of nordiazepam was observed at 1 hour. Plasma concentrations of nordiazepam were the highest and decreased monoexponentially. Plasma concentrations of the other drugs declined rapidly at first but more slowly later, and these data were analysed as biexponential models. In the analysis for metabolites, nordiazepam reached measurable levels after the injection of diazepam and clorazepate.

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“…Five male monkeys (Macaca mulatta) with a mean body weight of 11.3 (9.4 to 14.7) kg were trained on a delayed differentiation task (Konorski, 1959;Roberts & Bradley, 1967;Nicholson, Wright & Ferres, 1973). The task required each animal to differentiate between two visual stimuli, each of 2 s duration and separated by a 4 s delay, by pressing a lever during the presentation of the second stimulus if the stimuli were like (Go response) and to refrain from pressing the lever if the stimuli were unlike (No-Go response).…”

Section: Behavioural Studiesmentioning

confidence: 99%

β‐ADRENOCEPTOR ANTAGONISTS: STUDIES ON BEHAVIOUR (DELAYED DIFFERENTIATION) IN THE MONKEY (Macaca mulatta)

Nicholson

Wright

1980

British J Pharmacology

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IActivity of six ,B-adrenoceptor antagonists was studied on behavioural activity (delayed differentiation) in the monkey (Macaca mulatta). The drugs, three relatively lipophilic antagonists (propranolol, oxprenolol and metoprolol), and three relatively hydrophilic antagonists (acebutolol, atenolol and sotalol), were given by intraperitoneal injection (5 to 30 mg/kg). 2 With atenolol (25 to 30 mg/kg), total response time was increased, but there was no effect on the number of correct responses. With acebutolol (25 to 30 mg/kg), the number of correct responses was reduced, but there was no effect on total response time. With metoprolol (25 to 30 mg/kg), there was an increase in total response time and a decrease in the number of correct responses, and correct responses were decreased 4 h after injection over the whole dose range (5 to 30 mg/kg). 3 Some animals failed to respond or complete the task with 30 mg/kg oxprenolol, 25 mg/kg sotalol and 20 mg/kg propranolol. With 25 mg/kg oxprenolol, the total response time was increased and the number of correct responses was decreased. With 5-20 mg/kg sotalol, total response time was increased, but there was no effect on the number of correct responses. With 15 mg/kg of (±)propranolol and its isomers, there were increases in total response time and decreases in correct responses. 4 The studies suggest that lipophilic antagonists, such as propranolol, oxprenolol and metoprolol, are likely to have, at least, effects on the central nervous system, while hydrophilic antagonists may modify the peripheral nervous system. In the dose-ranges studied, propranolol had the greatest, and atenolol and acebutolol had the least effects. Atenolol and acebutolol may prove to be particularly useful in man when disturbances of the nervous system are to be avoided.

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Impaired performance on delayed matching in monkeys by heptabarbitone, pentobarbitone sodium and quinalbarbitone sodium

Cited by 22 publications

References 3 publications

Comparison of the residual effects of two benzodiazepines (nitrazepam and flurazepam hydrochloride) and pentobarbitone sodium on human performance.

Comparison of the residual effects of two benzodiazepines (nitrazepam and flurazepam hydrochloride) and pentobarbitone sodium on human performance.

BEHAVIOURAL AND PHARMACOKINETIC STUDIES IN THE MONKEY (Macaca mulatta) WITH DIAZEPAM, NORDIAZEPAM AND RELATED 1,4‐BENZODIAZEPINES

β‐ADRENOCEPTOR ANTAGONISTS: STUDIES ON BEHAVIOUR (DELAYED DIFFERENTIATION) IN THE MONKEY (Macaca mulatta)

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