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781.
M. Enquist B. Forkman T. Ljungberg 《Journal of neural transmission (Vienna, Austria : 1996)》1990,81(2):147-152
Summary Studies of the behavioural effects of benzodiazepines have focused in particular on situations with negative secondary stimuli, i.e., stimuli signalling negative primary events such as punishment or non-reward. The general result is that benzodiazepines attenuate behavioural reactions to this type of stimuli. The aim of the present study was to investigate if there are any differences between positive and negative secondary stimuli in this respect. Rats were treated with diazepam in a modified Skinner box with two levers. One of the levers always gave a small reward. A lamp being ON or OFF was used as a secondary stimulus indicating if the other lever would give a large or no reward. Pretreatment with diazepam (1.0 mg/kg) did not act differently on the response to the positive or negative secondary stimulus. The main effect was a general attenuation of optimal responding with a concomitant decrease in water intake. An alternative hypothesis stating that benzodiazepines alter the reactivity to secondary stimuli more in general is supported. 相似文献
782.
The daily administration of diazepam (10 mg/kg i.v.) in rats elicited tolerance to the sedative effect within 2-3 days, parallel to the emerging of a stimulatory syndrome. In the EEG, the latter was accompanied by a progressive replacement of the trains of spindles with 25-30 Hz low amplitude waves. No clear signs of tolerance to the myorelaxant effect of diazepam were observed. After 10 days of treatment, the drug was discontinued. Thereafter, a single administration of diazepam elicited a stimulatory syndrome and EEG desynchronization throughout the 15 days of withdrawal. [3H]diazepam binding studies, performed in frozen-thawed membrane preparations incubated at 37 degrees C for 30 min, showed a decrease of KD values in tolerant rats up to 7 days after discontinuation of the drug. In parallel, a reduction in the ability of GABA to enhance [3H]diazepam binding, as well as to protect [3H]diazepam recognition sites from thermoinactivation at 60 degrees C, were found in tolerant rats up to 15 days after drug termination. These data suggest that a modification in the regulatory activity of GABA on benzodiazepine recognition sites might underlie the tolerance to the sedative effects and EEG changes of benzodiazepines. 相似文献
783.
Pharmacokinetic and pharmacodynamic interactions of bretazenil and diazepam with alcohol 总被引:1,自引:1,他引:0
A. L. VAN STEVENINCK R. GIESCHKE R. C. SCHOEMAKER G. RONCARI B. TUK M. S. M. PIETERS D. D. BREIMER & A. F. COHEN 《British journal of clinical pharmacology》1996,41(6):565-573
1 Interaction between alcohol and bretazenil (a benzodiazepine partial agonist in animals) was studied with diazepam as a comparator in a randomized, double-blind, placebo controlled six-way cross over experiment in 12 healthy volunteers, aged 19−26 years.
2 Bretazenil (0.5 mg), diazepam (10 mg) and matching placebos were given as single oral doses after intravenous infusion of alcohol to a steady target-blood concentration of 0.5 g l−1 or a control infusion of 5% w/v glucose at 1 week intervals.
3 CNS effects were evaluated between 0 and 3.5 h after drug administration by smooth pursuit and saccadic eye movements, adaptive tracking, body sway, digit symbol substitution test and visual analogue scales.
4 Compared with placebo all treatments caused significant decrements in performance. Overall, the following sequence was found for the magnitude of treatment effects: bretazenil+alcohol>diazepam+alcohol≥bretazenil> diazepam>alcohol>placebo.
5 There were no consistent indications for synergistic, supra-additive pharmacodynamic interactions between alcohol and bretazenil or diazepam.
6 Bretazenil with or without alcohol, and diazepam+alcohol had marked effects. Because subjects were often too sedated to perform the adaptive tracking test and the eye movement tests adequately, ceiling effects may have affected the outcome of these tests.
7 No significant pharmacokinetic interactions were found.
8 Contrary to the results in animals, there were no indications for a dissociation of the sedative and anxiolytic effects of bretazenil in man. 相似文献
2 Bretazenil (0.5 mg), diazepam (10 mg) and matching placebos were given as single oral doses after intravenous infusion of alcohol to a steady target-blood concentration of 0.5 g l
3 CNS effects were evaluated between 0 and 3.5 h after drug administration by smooth pursuit and saccadic eye movements, adaptive tracking, body sway, digit symbol substitution test and visual analogue scales.
4 Compared with placebo all treatments caused significant decrements in performance. Overall, the following sequence was found for the magnitude of treatment effects: bretazenil+alcohol>diazepam+alcohol≥bretazenil> diazepam>alcohol>placebo.
5 There were no consistent indications for synergistic, supra-additive pharmacodynamic interactions between alcohol and bretazenil or diazepam.
6 Bretazenil with or without alcohol, and diazepam+alcohol had marked effects. Because subjects were often too sedated to perform the adaptive tracking test and the eye movement tests adequately, ceiling effects may have affected the outcome of these tests.
7 No significant pharmacokinetic interactions were found.
8 Contrary to the results in animals, there were no indications for a dissociation of the sedative and anxiolytic effects of bretazenil in man. 相似文献
784.
785.
D A Johnson 《Acta psychiatrica Scandinavica》1979,59(1):1-8
A double-blind trial of flupenthixol, nortriptyline and diazepam in neurotic depression using flexible dose schedules suggested that each drug is an efficient treatment for this category of depression although the patterns of response and prevalence of side-effects varied. No differences reaching a level of significance could be shown on rating scales of depression or anxiety, but trends favoured flupenthixol. However, clinical evaluation suggested flupenthixol to be more effective than diazepam on mental state examination (P less than 0.05) and to have a greater overall therapeutic effect than nortriptyline (P less than 0.05). It also had fewer side-effects than nortriptyline (P less than 0.05). 相似文献
786.
S. Högskilde J. W. Nielsen P. Carl H. Angelo M. Bredgaard Sörensen 《Acta anaesthesiologica Scandinavica》1987,31(4):289-291
The anticonvulsive activity (ED50), acute toxicity (LD50), and minimal neurotoxicity (TD50) of diazepam in an emulsion form (Diazemuls) were compared with two different water-based diazepam solutions (Valium and Stesolid). The diazepam preparations were administered intravenously to male mice. After determination of time of peak drug activity, the ED50's were established against pentetrazol-induced convulsions, at peak drug activity. The most important difference between the three diazepam preparations was a significantly higher LD50 of diazemuls (275 mg/kg) compared to valium (49 mg/kg) and stesolid (51 mg/kg). ED50 was: diazemuls 0.24 mg/kg, valium 0.14 mg/kg and stesolid 0.10 mg/kg. The therapeutic indices (LD50/ED50) were thus calculated to be 1146 for diazemuls, 350 for valium and 510 for stesolid. Time of peak drug activity and TD50 were equal for all three drugs. No signs of pain on injection or necrosis were observed following diazemuls, whereas this was common after valium and stesolid. 相似文献
787.
Summary The loss of isosorbide dinitrate from aqueous solutions stored in plastic infusion bags and/or infused through plastic giving
sets was investigated. During simulated infusions, the loss of isosorbide dinitrate was found to be flow-rate dependent. The
clinical and pharmacokinetic significance of this loss is discussed. Infusion of isosorbide dinitrate from a glass syringe
through high density polyethylene tubing overcame the loss associated with its adinistration via plastic infusion bags and
intravenous giving sets. This method was also applied successfully to minimise the previously reported loss of diazepam and
chlormethiazole during infusions. 相似文献
788.
The anticonvulsant activity of diazepam alone, or in combination with diphenylhydantoin was studied in pentylenetetrazol-, bicuculline- and isoniazid-induced Scizures. Alone, diphenylhydantoin did not influence the chemically-induced convulsions but enhanced the antipentylenetetrazol action of diazepam whilst failing to affect the protective effect of the benzodiazepine against bicuculline- and isoniazid-induced convulsions. It is suggested that a diphenylhydantoin-induced increase in the total number of specific benzodiazepine binding sites might be responsible for the enhancement of the antipentylenetetrazol activity of diazepam. The anticonvulsant action of diazepam against bicuculline and isoniazid-induced Scizures does not seem to involve an interaction with benzodiazepine receptors. 相似文献
789.
John W. Phillis 《Progress in neuro-psychopharmacology & biological psychiatry》1984,8(4-6):495-502
1. The hypothesis that inhibition of adenosine uptake may play an important role in the central actions of the benzodiazepines is presented.
2. The evidence supporting this hypothesis is discussed.
3. Brain concentrations of the benzodiazepines are adequate for inhibition of adenosine uptake.
4. Benzodiazepines, such as R015-1788 and R05-4864, which do not enhance γ-aminobutyric acid binding, may exert some of their central effects by inhibiting the uptake of adenosine. 相似文献
790.
O. M. Bakke K. Haram T. Lygre G. Wallem 《European journal of clinical pharmacology》1981,21(3):221-227
Summary Drug concentrations were measured in whole blood obtained from mother and child after induction of general anaesthesia with thiopental or diazepam and delivery by Caesarean section. In 27 cases given thiopental 3 mg/kg intravenously the 5-min child/mother concentration ratio rose with increasing injection-delivery (I-D) interval up to 8–10 min. The concentration in the newborn at 2 h showed a similar trend. In 30 cases given diazepam 0.3 mg/kg for sleep induction, there were some low values in cases delivered within 4 min after the injection. However, higher neonatal concentrations and child/mother ratios were observed when the operation lasted 4–5 min, and there was no further increase in cases with longer I-D intervals. There is evidence to suggest that net transfer to the fetus proceeds at a slower rate with thiopental than with diazepam. However, in the present series of low risk elective Caesarean sections, there was no appreciable difference between the induction agents with regard to their effect on the newborn infant. 相似文献