Preclinical pharmacology of midazolam.

Pieri, L.

doi:10.1111/j.1365-2125.1983.tb02267.x

Cited by 105 publications

(72 citation statements)

References 17 publications

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“…Unlike other reports (Pieri, 1983), midazolam did not cause any significant changes in the locomotor measures of the EPM at the doses used in this study, which excludes the possibility of bias in the results for any motor impairment that could be caused by a benzodiazepine drug. We also showed that 20 nmol of midazolam increased the escape threshold determined by direct electrical stimulation of the IC.…”

Section: Discussioncontrasting

confidence: 62%

Papel dos mecanismos GABAérgicos do colículo inferior e da substância cinzenta periaquedutal na interface sensoriomotora do medo e ansiedade

Saito¹

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Section: Discussioncontrasting

confidence: 62%

Papel dos mecanismos GABAérgicos do colículo inferior e da substância cinzenta periaquedutal na interface sensoriomotora do medo e ansiedade

Saito¹

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“…Although the initial animal studi minimal cardiovascular effects in thetized dog (Pieri, 1983;Hilfiker 1981) more pronounced cardiovasci have been reported in man (Hilfikei 1981;Forster, 1981;Muller et formed on both immediate and recent recall of these lists. This suggests that midazolam impairs the ability to acquire new memory more deeply ebo oal (o) than it impairs the sensorium or the ability to recall lists memorized before drug administrabetter than tion.…”

Section: Resultsmentioning

confidence: 99%

Midazolam: kinetics and effects on memory, sensorium, and haemodynamics.

Langlois

Kreeft

Chouinard

et al. 1987

Brit J Clinical Pharma

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1 This study aimed not only to compare the pharmacokinetics of oral and intravenous doses of the new water-soluble benzodiazepine, midazolam, but also to study the effects on haemodynamics, sensorium, and memory performance. 2 Eight normal human volunteers each received a single 15 mg dose of midazolam base orally and intravenously in randomized sequence 2 weeks apart. Serial venous samples were obtained for 12 h after dosing. Vital signs, sensorium testing and memory testing using word lists were also performed. Computerized non-linear least squares curve-fitting of the two-compartment open model to the oral and intravenous data simultaneously yielded the following estimates: VI, 0.331 kg-1, Vdss, 1.081 kg-1, t2,x, 0.10 h, t½2,z, 1.89 h, ka 1.17 h-1 and bioavailability, 49%. The intravenous dose decreased the systolic pressure 22 mm Hg during the first half-hour and the oral dose had 50% less effect. Most subjects became drowsy halfway through the infusion and were only rousable to voice by its end. The sensorium was clear by 2-3 h. After oral dosing the peak sensorium effects of ataxiadysarthria were seen at 30 min and had cleared by 2 h. Memory testing showed that memory acquisition was markedly impaired for at least 90 min after the intravenous dose and slight recovery was apparent at this time after the oral dose. Memory performance was proportionately more impaired than the sensorium score. 3 We conclude that: (a) midazolam kinetics are characterized by rapid absorption, but incomplete bioavailability and rapid elimination, (b) midazolam intravenously may lower blood pressure significantly, and (c) the level of consciousness correlates poorly with the degree of memory impairment.

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“…19.3,:1 The first dose of diazepam (3 mg'kg -~) probably produced a strong sedative effect onlyY The ratio of LDso of midazolam to LDso of diazepam equals 3.4. 36 For the first dose we used a slightly smaller ratio or, in others words, the first dose of diazepam (3 mg.kg-~) was probably somewhat higher than the first dose of midazolam (8 mg.kg-') in terms of toxicity, but probably lower in terms of hypnotic/sedative effects. However, later during the experiments the doses of the drugs were doubled and then tripled to observe the dose-related response within a wide spectrum of the effects of the anaesthesia induction drugs.…”

Section: Discussionmentioning

confidence: 99%