Theophylline antagonizes diazepam-induced psychomotor impairment

Henauer, S.; Hollister, Leo E.; Gillespie, H. K.; Moore, Frances

doi:10.1007/bf00542513

Cited by 26 publications

(6 citation statements)

References 18 publications

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“…Many studies agree in stating that sedation contributes to the amnesic effects of BZDs without, however, entirely explaining them (File and Bond, 1979;Roth et al, 1981). The use of centrally acting stimulants, such as caffeine or theophylline, decreases BZD-induced deficits of attention and, in parallel, increases psychomotor performance Mattila et al, 1982;Henauer et al, 1983;Roehrs et al, 1988;Johnson et al, 1990). However, a dissociation between the sedative and amnesic effects has often been observed, in particular with diazepam (George and Dundee, 1977;Rodrigo-Lusiardo, 1988) and lorazepam (Kothary et al, 1981;Patat et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

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Study of effects of clobazam and lorazepam on memory and cognitive functions in healthy subjects

Patat¹,

Klein²,

Surjus³

et al. 1991

Human Psychopharmacology

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This was a double-blind, placebo-controlled crossover study in 15 healthy female volunteers. It consisted of five sessions, separated by 1 week wash-out between sessions. The purpose of the trial was to study the potential amnesic and sedative activity of clobazam and lorazepam, and the potential antagonism between these effects under the joint influence of a high noise level and intense intermittent light stimulation (ILS), aimed at increasing the level of alertness. The study drugs were administered as a single daily oral dose. The amnesic and sedative effects were evaluated by objective measurements (digit span, Buschke selective reminding test, critical flicker fusion, reaction time, tapping, mental arithmetic test) and subjective measurements (visual analogue scale and adverse effect questionnaire) before each administration, then 1 h, 2 h, 2 5 h, 3 h, 4 h and 7 h post-dosing. An analysis of variance according to a balanced Latin square design was performed. Clobazam, at a dosage of 10 mg, was devoided of sedative and amnesic effects; at a dosage of 30 mg it induced only moderate memory disturbances. In contrast, lorazepam, administered at doses of 1 and 3 mg, produced marked and dose-dependent disturbances of memory, alertness and cognitive functions. The use of visual and sound stimuli, designed to increase the level of alertness, did not counteract the sedative effects induced by lorazepam.

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Section: Discussionmentioning

confidence: 99%

“…Similarly, the results of clinical pharmacology studies show that central nervous stimulants such as caffeine or theophylline are capable of attenuating or counteracting disturbances of attention and/ or performance after ingestion of diazepam Mattila et al, 1982;Henauer et al, 1983;Roehrs et a/., 1988;Johnson et al, 1990).…”

Section: Introductionmentioning

confidence: 98%

Study of effects of clobazam and lorazepam on memory and cognitive functions in healthy subjects

Patat¹,

Klein²,

Surjus³

et al. 1991

Human Psychopharmacology

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“…These attempts might be clinically helpful, if recovery time or residual effects have to be minimized. Conflicting data have been reported for physostigmine (Avant et al, 1979;Grote et al, 1981;Pandit et al, 1983) and the observed effects of theophylline (Arvidsson et al, 1982;Henauer et al, 1983) might be due to ethylenediamine which is part of the aminophylline preparation used and which is known to interact with the binding of [3H]-diazepam in cerebral cortical synaptosomal membranes (Morgan & Stone, 1983). The new imidazodiazepine Ro 15-1788 can reverse the sedative effects of 3-methylclonazepam (Darragh et al, 1981), diazepam (Darragh et al, 1982), flunitrazepam (Gaillard & Blois, 1983) and midazolam (Klotz et al, 1984a).…”

Section: Introductionmentioning

confidence: 98%

Flunitrazepam and lormetazepam do not affect the pharmacokinetics of the benzodiazepine antagonist Ro 15‐1788.

Klotz¹,

Duka²,

Dorow³

et al. 1985

Brit J Clinical Pharma

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Following a single intravenous dose of 0.1 mg/kg, the pharmacokinetics of Ro 15‐1788, a specific benzodiazepine antagonist, have been investigated in 20 healthy male volunteers. In random order injection of Ro 15‐1788 has been preceded (5 min) by intravenous dosing with 0.06 mg/kg of lormetazepam (n = 6), 0.03 mg/kg of flunitrazepam (n = 8) or placebo (n = 6). The rapid elimination of the antagonist could be characterized by an elimination half‐life between 0.9 to 1.4 h and a total plasma clearance of 727 to 1440 ml/min. These single dose studies indicate that the disposition of Ro 15‐1788 was not affected by the acute coadministration of both benzodiazepines.

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“…Enforced maintenance of prolonged wakefulness for more than 15 min during a nocturnal learning test significantly increased the duration of the consolidation phase, and significantly reduced triazolam amnesia the following morning. Similarly, central stimulants such as caffeine or theophylline attenuate or antagonize the deficits of attention or performance observed after diazepam intake (Mattila et al, 1982;File et a/., 1982;Henauer et a/., 1983).…”

Section: Discussionmentioning

confidence: 99%

Study of the potential pharmacodynamic antagonism of RU 41 656 on scopolamine and triazolam impairment in healthy subjects

Patat¹,

Klein²,

Surjus³

et al. 1990

Human Psychopharmacology

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The potential improvement on attention and memory of a single oral does of R U 41 656, and the potential antagonism of the deficits of these functions induced by oral administration of scopolamine 1 mg and triazolam 0.5 mg, have been investigated in a six-period, placebo-controlled, double-blind, crossover study involving 12 healthy young volunteers. The effects of the compounds were evaluated by objective test (Buschke selective reminding test, CFF, simple and multiple-choice reaction time, tapping, arithmetical calculation, DSST) and subjective measurements (visual analogue scale, side-effects questionnaire). Measurements were taken before treatment and 2, 4 and 7 h after R U 41 656 intake. Neither placebo alone nor R U 41 656 alone modified the performances of these subjects. Under the experimental conditions of the trial, scopolamine given orally did not cause the disturbances of attention and memory usually described. On the contrary, triazolam caused a pronounced impairment of vigilance and memory. R U 41 656 did not antagonize the sedative effects of triazolam, but partially attenuated its amnesic effects.

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Theophylline antagonizes diazepam-induced psychomotor impairment

Cited by 26 publications

References 18 publications

Study of effects of clobazam and lorazepam on memory and cognitive functions in healthy subjects

Study of effects of clobazam and lorazepam on memory and cognitive functions in healthy subjects

Flunitrazepam and lormetazepam do not affect the pharmacokinetics of the benzodiazepine antagonist Ro 15‐1788.

Study of the potential pharmacodynamic antagonism of RU 41 656 on scopolamine and triazolam impairment in healthy subjects

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