Sedative Effects and Impaired Learning and Recall After Single Oral Doses of Lorazepam

Shader, Richard I.; Dreyfuss, D; Gerrein, John R.; Harmatz, Jerold S.; Allison, S. J.; Greenblatt, David J.

doi:10.1097/00132586-198702000-00035

Cited by 11 publications

(16 citation statements)

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“…(Boulenger et al, 1989). In the same experiment like in the present one the RAVLT was not sensitive enough to detect BZD-induced impairment in verbal learning or memory despite several reports demonstrating the negative effects of either triazolam (0.5 mg) (Klein et al, 1986) or lorazepam (1.5-3 mg) on this test (Shader et al, 1986).…”

Section: S C T (B)supporting

confidence: 40%

Repeated administration of buspirone: Absence of pharmacodynamic or pharmacokinetic interaction with triazolam

Boulenger

Gram

Jolicoeur

et al. 1993

Human Psychopharmacology

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The present study was designed to evaluate possible phannacokinetic and pharmacodynamic interactions between buspirone administered repeatedly and triazolam given acutely. Ten healthy male volunteers participated in the study and received 0.25 mg of triazolam orally after a one-week pretreatment with either placebo or buspirone 5 mg t.i.d. The study design was double-blind and crossover, the subjects receiving two times triazolam after the random administration of buspirone or placebo, each treatment period being separated by a washout period of 1 week. Plasma triazolam concentrations were measured by a radio-receptor assay using 'H-flunitrazepam as radioligand. Psychomotor effects of triazolam were measured through subjective self rating scales and various cognitive tests exploring concentration, memory and psychomotor skills.Overall, the results of the study failed to demonstrate any significant difference in triazolam subjective or objective effects as well as in triazolam plasma concentrations after a one-week pretreatment with either placebo or buspirone 15 mg daily. They do suggest that clinically relevant interactions are unlikely to appear when buspirone at moderate dosage is co-prescribed with acute doses of triazolam, though these data do not exclude the possibility of pharmacokinetic interactions between the two drugs. Finally our data also suggest the need for more specific studies in order to demonstrate a possible improvement of psychomotor functions after buspirone administration.

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Section: S C T (B)supporting

confidence: 40%

Repeated administration of buspirone: Absence of pharmacodynamic or pharmacokinetic interaction with triazolam

Boulenger

Gram

Jolicoeur

et al. 1993

Human Psychopharmacology

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“…Although in other studies the results of the Weingartner cognitive maps appeared to deteriorate after administra tion of various psychotropic agents [24,40], a recent study demonstrated that DZP (10 mg) had only limited effects on this test [41], except when administered intra venously [42]. Whereas RAVLT results have been signif icantly impaired in studies using other BZD, [43,44], it is noteworthy that several investigators have suggested that DZP and its metabolite Nor-DZP may have limited amnestic properties when compared to shorter half-life BZD or to those having a higher affinity for central receptors [11,17,38].…”

Section: Discussionmentioning

confidence: 99%

Buspirone and Diazepam: Comparison of Subjective, Psychomotor and Biological Effects

et al. 1989

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The effects of oral buspirone (BUS, 10 mg) and diazepam (DZP, 10 mg) were studied in 12 healthy women volunteers using subjective ratings, objective tests of psychomotor and cognitive functions and urinary dosage of catecholamine output. Drugs were randomly administered to the same subjects, in a crossover, double-blind study, each drug administration being separated by at least 1 week. BUS subjective effects were less severe than those of DZP and not accompanied by feelings of sleepiness that characterized DZP sedative effects. Furthermore, BUS did not impair psychomotor functioning while DZP induced both an impairment of central sensory processing and, to a lesser extent, an impairment in delayed memory.

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“…The effects of triazolam on information acquisition and recall are consistent with the recognized syndrome of benzodiazepine-induced anterograde amnesia. 7,10,18,24,27,[50][51][52] In all 6 study cohorts, initial acquisition and immediate recall of information presented at 1.5 hours after dosing were modestly but significantly impaired by triazolam compared with placebo. However, triazolam generally impaired storage of the acquired information, assessed as free recall (delayed recall) of the same information at 24 hours after dosing.…”

Section: Discussionmentioning

confidence: 99%

“…Acquisition and recall of information were evaluated with the use of a word-list free-recall procedure that was administered at 1.5 hours after drug or placebo administration. 7,10,18,19,[22][23][24][25][26][27] Sixteen words, taken from 4 different categories, were read in random order in "shopping-list" fashion. Subjects wrote down items immediately after lists were presented in random order.…”

Section: Fig 2 Relationship Between Age and Triazolam Oral Clearancementioning

confidence: 99%

Age and gender effects on the pharmacokinetics and pharmacodynamics of triazolam, a cytochrome P450 3A substrate

Greenblatt

Harmatz

Moltke

et al. 2004

Clinical Pharmacology & Therapeutics

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Sixty-one healthy men and women, aged 20 to 75 years, received single 0.25-mg doses of triazolam, a cytochrome P450 (CYP) 3A substrate benzodiazepine, and placebo in a double-blind crossover study. Among women, age had no significant effect on area under the triazolam plasma concentration curve (AUC) (Spearman r=0.14, P=.44) or clearance (r =-0.09, P=.62). Among men, AUC increased (r=0.43, P <.02) and clearance declined (r=-0.42, P <.02) with increasing age. Gender differences in triazolam kinetics were not apparent. Compared with placebo, triazolam impaired digit-symbol substitution test performance, increased observer-rated sedation, impaired delayed recall of information learned at 1.5 hours after dosing, and increased electroencephalographic beta amplitude. Among men, mean values of relative digit-symbol substitution test decrement (P <.002) and observer-rated sedation (P <.05) were significantly greater in elderly subjects compared with young subjects. Age-dependent differences among women reached significance for observer-rated sedation (P <.02). A combination of higher plasma levels and increased intrinsic sensitivity explained the greater pharmacodynamic effects of triazolam in elderly subjects. Although the findings are consistent with reduced clearance of triazolam in elderly men, individual variability was large and was not explained by identifiable demographic or environmental factors.

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Sedative Effects and Impaired Learning and Recall After Single Oral Doses of Lorazepam

Cited by 11 publications

References 0 publications

Repeated administration of buspirone: Absence of pharmacodynamic or pharmacokinetic interaction with triazolam

Repeated administration of buspirone: Absence of pharmacodynamic or pharmacokinetic interaction with triazolam

Buspirone and Diazepam: Comparison of Subjective, Psychomotor and Biological Effects

Age and gender effects on the pharmacokinetics and pharmacodynamics of triazolam, a cytochrome P450 3A substrate

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