Time course of the effects of diazepam and lorazepam on perceptual priming and explicit memory

The effects of diazepam and lorazepam on explicit memory and perceptual priming were studied 50, 130 and 300 min after drug administration. Sixty healthy volunteers were randomly assigned to one of five parallel groups (placebo, diazepam 0.2 or 0.3 mg/kg, lorazepam 0.026 or 0.038 mg/kg). The corresponding doses of benzodiazepines exerted a similar negative effect on explicit performance. Lorazepam markedly impaired priming performance, whereas the effect of diazepam was intermediate between that of placebo and that of lorazepam 0.038 mg/kg. The impairment was maximal at the theoretical peak plasma concentration. Contamination by explicit memory could account for the decrease in priming performance observed in the diazepam groups.     

Treatment of Status Epilepticus

Summary: Status epilepticus, particularly the convulsive form, is a medical emergency, warranting prompt and aggressive treatment. To do this, one must have a thorough understanding of the pharmacology of the anticonvulsant agents. Therapy should be directed toward rapid termination of the status epilepticus, prevention of seizure recurrence, and treatment of any underlying cause. Most importantly, one should establish and adhere to a standard treatment protocol for best results.     

Effects of lorazepam upon recollective experience in recognition memory

The effects of lorazepam (2 mg) and placebo upon recognition memory with and without conscious recollection were assessed in a cross-over study with normal volunteers. When recognising a word from study lists presented before and 1, 3 and 5 h after drug administration, subjects were required to indicate whether they could consciously recollect the word's prior occurrence or recognised it on the basis of knowing; in the absence of conscious recollection. Lorazepam only impaired word recognition which was accompanied by conscious recollection, and further, the level of this impairment correlated significantly with each of three different indices of subjects' arousal at the time of presentation of each list. Recognition in the absence of conscious recollection was not impaired but somewhat heightened by lorazepam, and these effects did not significantly relate to any index of arousal. These findings are interpreted as providing further support for the notion that recognition entails two distinct components, one based on contextual and associative information and related to conscious recollection, the other possibly based on a traceless perceptual or semantic memory system and related to feelings of knowing in the absence of conscious recollection. Implications are drawn for a contextual-encoding/retrieval account of lorazepam-induced amnesia.     

Effects of benzodiazepine receptor ligands on the performance of an operant delayed matching to position task in rats: opposite effects of FG 7142 and lorazepam

The effects of a series of benzodiazepine (BZ) receptor ligands, ranging from a full agonist through to partial inverse agonists, were examined on short term working memory in the rat. The behavioural paradigm used was a discrete trial, operant delayed matching to position task, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. The benzodiazepine receptor (BZR) full agonist lorazepam (0.25, 0.375 and 0.5 mg/kg) dose and delay dependently impaired matching accuracy. Lorazepam also increased the latency to respond and decreased the number of nose pokes made into the food tray during the delays. In contrast, the BZR partial agonist ZK 95 962 (1, 3, 10 mg/kg) did not affect matching accuracy, but did increase the speed of responding. The BZR antagonist ZK 93 426 (1.25, 5, 25 mg/kg) had no effects in this paradigm. The BZR weak partial inverse agonists Ro 15-4513 (0.1, 1 and 10 mg/kg) and ZK 90 886 (1, 3 and 10 mg/kg) did not affect accuracy of performance. However, both of these drugs increased the latency to respond and decreased nose poke responses. These motoric effects were particularly strong following 10 mg/kg Ro 15-4513. This shows that the effects of drugs on the accuracy of responding and on the speed of responding can be dissociated. The BZR partial inverse agonist FG 7142 had effects on matching accuracy that were dependent upon dose. The lowest dose of FG 7142 (1 mg/kg) significantly improved accuracy, whereas the highest dose (10 mg/kg) impaired accuracy. This impairment induced by FG 7142 (10 mg/kg) was accompanied by an increase in the latency to respond and a decrease in the number of nose pokes. Taken together, these results show that the accuracy of delayed matching performance can be modulated in opposite ways by the BZR full agonist lorazepam and a low dose of the BZR partial inverse agonist, FG 7142.     

Benzodiazepines alter acquisition and retention of an inhibitory avoidance response in mice

These experiments were performed to examine the effects of graded doses of diazepam, flurazepam, or lorazepam given to Swiss-Webster mice either 30 min prior to training or immediately after training in a one-trial inhibitory (passive) avoidance task. A 350 A footshock was administered following entry into a darkened compartment and retention was tested three days later. Doses of 10.0 mg/kg diazepam and 20.0 mg/kg lorazepam given before training significantly impaired acquisition, while 1.0 mg/kg flurazepam, given immediately after training, produced retrograde amnesia. These results indicate that benzodiazepines affect memory processes and that various drugs of the benzodiazepine family differentially affect acquisition and memory consolidation.     

Section B Review of two years clinical experience with lorazepam

Summary

Lorazepam has been used during the past two years to treat approximately 250 hospital patients suffering from symptoms of anxiety and tension. In-patients and outpatients of all ages have been treated. The average dosage range was 0.5 to 5?mg. lorazepam t.d.s. The highest daily dose was 30?mg.; the longest duration of treatment almost 2 years. Distinct improvement in symptoms such as anxiety, restlessness, agitation, tension, irritability and insomnia has been noted in about 70% of patients with very few side-effects. Typical case histories are discussed. It is concluded that lorazepam is an effective, extremely well-tolerated drug, particularly suitable for out-patients provided the dosage is carefully adjusted.     

Section A Clinical pharmacological studies on lorazepam

Summary

Lorazepam, in doses sufficient to impair the critical flicker frequency, disc-dotting performance, reaction times or visuomotor co-ordination did not influence visual function, implying a specific CNS action for this agent.     

Section C Lorazepam as a premedicant for general anaesthesia

Abstract

Two studies are described, an open study on the degree of sedation produced by lorazepam and its effects on memory recall; and a double-blind study comparing lorazepam with heptabarbitone and diazepam. Overall, lorazepam has proved to be an interesting agent in premedication. It has many of the attributes of the narcotics -good sedation, good effect on memory recall and some post-operative basal narcosis which is of advantage in major operations. On the other hand, in the doses used it appears to have little effect on the cardiovascular system and is less likely to cause post-operative nausea and vomiting than the narcotic group.     

抗焦虑对胃癌根治术患者七氟烷用量及术后恢复的影响

目的:研究劳拉西泮联合咪达唑仑对择期胃癌根治术患者抗焦虑作用的有效性,及该方法对术中七氟烷用量和术后疼痛的影响.方法:观察组手术前1d服劳拉西泮,术前40min静注咪达唑仑,术中BIS监测控制麻醉深度,观察两组患者术前Spielberge状态—特质焦虑问卷(STAI)评分,术中七氟烷用量,麻醉恢复时间及术后2、6、24h疼痛VAS评分.结果:观察组状态-特质焦虑问卷评分低于对照组(S-AI:53.60±4.45vs62.70±3.98,P<0.05;T-AI:54.78±3.97vs65.65±4.21,P<0.05),七氟烷的使用量少于对照组(34.70±0.46vs36.20±0.44,P<0.05).两组术后苏醒及拔管时间无统计学差异.两组患者术后6、24hVAS评分,观察组低于对照组(6hVAS评分:3.45±1.60vs4.89±1.91,P<0.05;24hVAS评分:3.51±1.76vs5.17±1.71,P<0.05).结论:劳拉西泮联合咪达唑可以减轻术前患者的焦虑状态,减少术中七氟烷的使用,有利于减轻患者术后疼痛.     

Catatonia: short-term response to lorazepam and dopaminergic metabolism

Therapeutic response to lorazepam and dopaminergic metabolism were investigated in 18 neuroleptically naive acute catatonic patients. They were diagnosed as catatonic according to criteria by Lohr and Rosebush and treated exclusively with lorazepam (2–4 mg) during the first 24 h. Dopaminergic metabolism (plasma HVA, plasma MHPG), anxiety (HAM-A) and parkinsonic/dyskinetic movements (SEPS, AIMS) were measured under standard conditions before initial treatment with lorazepam (day 0) and 24 h after initial treatment (day 1). On day 0 responders to lorazepam treatment (complete remission of catatonic syndrome after 24 h according to Rosebush and Lohr) showed significantly higher (P=0.004) plasma HVA (130.4±51.2 pmol/ml; means ± SD) than non-responders (no remission of catatonic syndrome after 24 h; 73.2±40.5 pmol/ml; means ± SD). On day 1 plasma HVA did not differ any more significantly between both groups Clinically, responders showed significantly higher HAM-A (P=0.025) and AIMS (P=0.022) scores as well as significantly lower SEPS (P=0.049) scores than non-responders on day 0. Hence catatonic short-term responders and non-responders to lorazepam can be distinguished with regard to plasma HVA, anxiety and dyskinetic/parkinsonic movements.