Ro 15–1788 Antagonizes the Effects of Diazepam in Man Without Affecting Its Bioavailability

O'Boyle, Ciaran; Lambe, R.; Darragh, A.; Taffe, W.; Brick, I.; Kenny, Marie

doi:10.1093/bja/55.4.349

Cited by 82 publications

(19 citation statements)

References 19 publications

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“…Work on human subjects has shown that Ro 15-1788 is able to block the predicted effects of benzodiazepines whether given prior to (Gath et al 1984), simultaneously with (Ismail et al 1981;Gaillard and Blois 1983;Darragh et al 1981Darragh et al , 1982aO'Boyle et al 1983) or subsequent to benzodiazepine administration (Ismail etal. 198l;Ziegler and Schalch 1982;Laurian et al 1984).…”

mentioning

confidence: 99%

The effects of the benzodiazepine antagonist Ro 15-1788 on psychophysiological performance and subjective measures in normal subjects

1986

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Ro 15-1788 is an imidazodiazepine which was initially described as a pure benzodiazepine antagonist lacking in intrinsic actions. Although recent animal work has shown the drug to have differing intrinsic actions depending on the dose, the majority of studies on human subjects conclude that it is a pure antagonist of benzodiazepines. Two oral doses of Ro 15-1788 (30 mg and 100 mg) were compared with 5 mg diazepam and placebo in their intrinsic effects on a range of psychophysiological, performance and subjective measures in 12 healthy adult subjects. At both these doses Ro 15-1788 showed a mixture of agonist (benzodiazepine-like) effects and other non-benzodiazepine-like effects on the variables measured. Although there was no clear-cut dose-response relationship, the results suggested a predominance of benzodiazepine-like effects at the higher dose on physiological measures whilst the lower dose was observed to have greater effects on a number of behavioural and subjective dimensions. The subjective changes were the opposite of those normally found for benzodiazepines.

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confidence: 99%

The effects of the benzodiazepine antagonist Ro 15-1788 on psychophysiological performance and subjective measures in normal subjects

1986

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“…The present findings, combined with previous evidence that flumazenil blocks or reverses CDP-induced impairment of successive discrimination [Cole, 1989a1, suggest that mediation mechanisms of the BDZ drug class may also share common properties. Additional evidence that flumazenil partially blocks or reverses BDZinduced impairment of learning in tasks markedly different from the present one [Bonetti et al, 1982;O'Boyle et al, 1983;Thiebot et al, 19831 suggests that central BDZ receptors may play an even more generalized (but not necessarily exclusive) role in mediating drug-induced impairment.…”

Section: Discussionmentioning

confidence: 53%

Reversal of diazepam‐induced impairment in successive discrimination performance by flumazenil

Cole

1992

Drug Development Research

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The effects of diazepam (DZ) alone and in combination with flumazenil (Ro 15-1 788) on the performance of a previously learned successive discrimination task were studied in male Sprague-Dawley rats. DZ 4 mg/kg impaired discrimination performance in five successive sessions, although animals showed some tolerance to the drug's action. The impairment in discrimination performance was due to an increase in responding during no go periods of the task (errors of commission). The benzodiazepine (BDZ) receptor antagonist flumazenil (5 and 10 mg/kg) partially reversed the impairment in discrimination performance and reduced the number of incorrect responses in a generally dose-dependent manner when coadministered with DZ. These findings suggest that the impairment in discrimination performance by DZ is mediated by central BDZ receptor sites. When administered alone, flumazenil 10 mg/kg (but not 5 mg/kg) produced a mild impairment in discrimination performance which, in contrast to DZ's effects, was due to both small increases in no go period responses (errors of commission) and small decreases in go period responses (errors of omission). These findings suggest that flumazenil is not a neutral antagonist but has some intrinsic action of its own. o 1992 Wiley-Liss, Inc.

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“…1977;Snyder el al.. 1977;Wolkowitz and Tinklenberg, 1985;Wolkowitz et al, 1985c], The BZD recep tor (which is functionally linked to the GABA receptor, cf. Paul et al [1981], Wolkowitz and Paul [1985]) is directly implicated in these effects since Ro 15-1788, a BZD receptor antagonist without intrinsic activity, blocks the BZD-induced amnesia [O'Boyle et al, 1983]. Many studies implicate the encoding or consolidation phase of memory processing rather than initial registra tion or subsequent retrieval, as being vulnerable to the BZD's disruptive effects [Ghoneim and Mewaldt, 1975;Frumin et al, 1976].…”

Section: Catecholaminesmentioning

confidence: 99%

A Psychopharmacological Perspective of Cognitive Functions

Wolkowitz

Tinklenberg

Weingartner³

1985

Neuropsychobiology

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In this article we review the effects of specific drugs or neurotransmitter systems on cognitive functions. While much of what we know about drugs’ effects on memory is derived from animal experiments, this review focusses on studies relevant to human clinical conditions. We conclude with a speculative analysis or taxonomy of the pharmacology of memory which broadly highlights the utility of viewing memory as being comprised of several differentiated processes.

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Ro 15–1788 Antagonizes the Effects of Diazepam in Man Without Affecting Its Bioavailability

Cited by 82 publications

References 19 publications

The effects of the benzodiazepine antagonist Ro 15-1788 on psychophysiological performance and subjective measures in normal subjects

The effects of the benzodiazepine antagonist Ro 15-1788 on psychophysiological performance and subjective measures in normal subjects

Reversal of diazepam‐induced impairment in successive discrimination performance by flumazenil

A Psychopharmacological Perspective of Cognitive Functions

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