摘要:

Rebound insomnia and rebound anxiety are clinical conditions related to withdrawal of certain benzodiazepine drugs. Numerous studies of benzodiazepine and nonbenzodiazepine hypnotics conducted in our sleep laboratory demonstrated that rebound insomnia developed following withdrawal from benzodiazepines with a rapid or intermediate elimination rate. Several studies conducted by other investigators also indicated the development of rebound insomnia under similar conditions. Rebound insomnia and rebound anxiety are discussed in terms of their interrelationship, clinical implications, and receptor mechanisms. Evidence suggests that drugs producing rebound insomnia and rebound anxiety also show a more rapid development of tolerance and greater potential for drug dependence than benzodiazepines where the parent compound or its metabolites have a long elimination half-life.

ISSN:0031-7012    

DOI:10.1159/000137794

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

Midazolam, an investigational hypnotic, was evaluated for effectiveness, side effects, and withdrawal phenomena in doses of 10, 20, and 30 mg in three separate sleep laboratory studies, each including 4 placebo-baseline nights, 7 drug nights, and 3 placebo-withdrawal nights. Only a slight to moderate degree of effectiveness was shown across the three doses; this effectiveness was much more pronounced during the first third of the night. There was no dose-response effect for effectiveness with either initial or continued drug administration. In general, there was less effectiveness on the last 3 drug nights, indicating a potential for the development of tolerance over a relatively short period of time. Following withdrawal there was a marked dose-related worsening of sleep above baseline levels (rebound insomnia).

ISSN:0031-7012    

DOI:10.1159/000137795

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

It has been suggested that large cerebral arteries contribute to cerebral vascular resistance and thus participate actively in the regulation of cerebral blood flow (CBF) during changes in arterial carbon dioxide tension (PCO2). In order to test this hypothesis, 3-cm segments of carotid artery from adult male rabbits were studied. The segments were mounted in a chamber with constant surrounding pressure and temperature and perfused at constant pressure. Inflow pressure, outflow pressure, and outflow rate were measured and values of resistance (R) were calculated before (C) and after stimulation with two sequential norepinephrine concentrations: 4 × 10–6M (NE1), 1 × 10–5M (NE2). During each sequence, the PCO2 of the surrounding and perfusion media were held equal and constant at one of four levels. The following mean R values were obtained:PC02, mm HgCNE1NE2

ISSN:0031-7012    

DOI:10.1159/000137796

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

Hyperosmotic sucrose solutions elicited tension from rat aortic strips in direct proportion to osmolarity. Norepinephrine-induced tension was reduced in proportion to increases in osmolarity; however, reduction of barium-induced tension by hyperosmolar solutions was minimal. Norepinephrine-induced tension is primarily dependent on intracellular calcium mobilization, while barium-induced tension is primarily dependent on extracellular calcium influx. Therefore, hyperosmolar solutions may alter vasoconstriction associated with intracellular calcium mobilization rather than that associated with extracellular calcium influx. In the presence of verapamil which blocks calcium entry into muscle, barium-induced tension was eliminated while the direct tension elicited by hyperosmolar solutions was slightly affected (6 % reduction) and the inhibitory effect of hyperosmolar solutions on norepinephrine-induced tension was still observed. In contrast, the tension elicited by hyperosmolar solutions was greatly reduced by papaverine which promotes sequestration of myoplasmic calcium to cause relaxation. The vascular effects of hyperosmolar solutions may be due to alterations in the intracellular calcium rather than the extracellular calcium utilized by vasoconstricting agents.

ISSN:0031-7012    

DOI:10.1159/000137797

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

Disulfiram has been shown to decrease the incidence of arrhythmias in rabbits exposed to trichloroethylene. In this study additional cardiotoxic models were used to evaluate disulfiram’s antiarrhythmogenicity. Disulfiram (7.5 mg/kg, i.v.) significantly decreased the time spent in arrhythmia compared to control rabbits, 120–180 s following intravenous administration of 4 mg/kg barium chloride. This was very similar to the effect of quinidine sulfate (10 mg/kg, i.v.) used as a positive control. In ouabain-induced arrhythmias, disulfiram treatment (400 mg/kg, i.p.) did not significantly alter the arrhythmogenic or lethal doses of a ouabain infusion. Quinidine, however, significantly increased the arrhythmogenic dose 86% and the lethal dose 44% compared to control. In vitro studies demonstrated that disulfiram (1 × 10–4 and 3 × 10–4M) significantly depressed the myocardial contractility of rat ventricular strips compared to polyethylene glycol 400

ISSN:0031-7012    

DOI:10.1159/000137798

出版商:S. Karger AG    

年代:1983

数据来源: Karger

摘要:

The structure activity correlation of several groups of anthranilic acid derivatives was studied. 59 compounds, most of them possessing the anthranilic acid moiety, were synthesized and tested for diuretic and saluretic activities. Equations correlating the biological activities of these compounds with their physicochemical constants suggest positive dependence of the diuretic activity on log P (octanol: water partition coefficient). It is concluded that, within limits, the variation in biological activity is primarily governed by the lipophilicity of the molecule, and further increase in log P value will not enhance this activity.

ISSN:0031-7012    

DOI:10.1159/000137799

出版商:S. Karger AG    

年代:1983

数据来源: Karger