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A young nurse was found dead in a bathtub. An autopsy revealed the following results: pulmonary emphysema, severe edema of both lungs, transudation in both pleural cavities. Conspicuous were skin sticks of a white wax material. In chemical-toxicological analysis diazepam, tetrazepam and phenobarbital were detected in this material. After anal-rectal and additionally oral ingestion the following blood concentrations were determined: BAC 0.03/1000; diazepam 500 ng/ml; nordiazepam 65 ng/ml; tetrazepam 180 ng/ml; phenobarbital 9.4 mg/l. In connection with this drug effects an acute, multifocal, suppurating bronchopneumonia in both lungs was revealed as the cause of death.

It has been demonstrated in rat experiments that intraperitoneal injection of 100 mg/kg phenazepam immobilizes the animals for one hour, causes long-term diminution of the muscular tonus and disturbed coordination of movements, tachycardia, hypotension, hyperthermia, depression of orientation and exploration motor activity, and disturbance of conditioned reflexes of active and passive avoidance. It is concluded that the changes in the above-indicated parameters of autonomic and behavioral status of rats under the effect of a 100 mg/kg dose of phenazepam are clearly expressed for a long period of time, are specific to the effect of benzodiazepines and may therefore serve as a model of severe BD intoxication for evaluating the efficacy of their antidotes. This has been confirmed in experiments with the well-known BD antagonist phlumazelin.

Even though acute poisonings with benzodiazepines are extremely common, less is known of the clinical toxicity of recent derivatives, particularly in children. 1,989 cases involving ethyle loflazepate, flunitrazepam, prazepam or triazolam recorded at the Lyons Poison Center and due to 1 compound and associated with clinical symptoms were selected for study. Children less than 16-y of age accounted for 482 cases. Sleepiness, agitation and ataxia were significantly more frequent in the children. Hypotonia was seldom observed but was indicative of severe poisoning. The dangerous toxic dose of these compounds in children is suggested to be 0.78-0.90 mg ethyle loflazepate/kg, 0.26-0.29 mg flunitrazepam/kg, 7.80-9.00 mg prazepam/kg and 0.06-0.07 mg triazolam/kg. These results are in keeping with the relatively low acute toxicity of the older benzodiazepines.

Necrotizing arteritis and periarteritis were found in Beagle and German Shepherd dogs treated for 13 or 52 weeks with the novel benzodiazepine receptor (BZR) partial agonist Ro 16-6028 (generic name bretazenil). Eight male and one female out of a total of 20 dogs treated with 40-60 mg/kg/day Ro 16-6028 developed the arteritis, predominantly in the heart or the epididymis. Two of these animals died prematurely following treatment at the initial dosing levels of 80 and 55 mg/kg/day; one of these two dogs was asymptomatic and in good general condition until death. Clinically, all but one of the dogs showed sedation, ataxia, stiff gait, body weight-loss and a deterioration of the general condition as well as changes of some laboratory parameters. No signs of arteritis and untoward clinical or laboratory findings were seen at lower doses. Possible aetiologies, as well as the mechanisms involved in arteritis in general and the genetic disposition of beagles in particular for this type of effect, are discussed. Reflections on the potential risk to man of this so far unknown finding after oral treatment with 1,4-benzodiazepines (BZs) are presented.

The authors report the case of an eleven-month old infant who was given maprotiline and clobazam. He was found in coma state and suffered from convulsions, that were treated with phenobarbital. The electrocardiogram showed a right bundle branch block and a left anterior hemiblock over 72 h. The child then recovered without sequelae.

Cyclic coma in a 4-year-old boy followed an ingestion of clonazepam, a new benzodiazepine, utilized in treatment of convulsive disorders. Alternation between coma and a hyperalert state occurred even after further gastrointestinal absorption had, presumably, been precluded. Laboratory identification by routine examination for benzodiazepines was unsuccessful.