Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “DIAZEPAM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMedDate not supplied

Aging: changes in distribution of diazepam and metabolites in the rat.

The brain levels of diazepam and its metabolites after a single iv injection of diazepam were measured over a 2-hr time period in young (3-4-month-old), mature (12-15-month-old), and senescent (29-31-month-old) male Fischer 344 rats. The areas under the brain level time curves were used as an index of exposure. Senescent rats were exposed to significantly more diazepam, N-desmethyldiazepam, and oxydiazepam between 0 and 120 min after an injection of 180 micrograms/kg of diazepam than the young or mature animals. The unbound plasma level failed to adequately account for the age-related increase in brain exposure to diazepam. Mechanisms other than the unbound diazepam in plasma are probably involved in eliciting the age-associated increase in brain levels of diazepam and its metabolites.

Aging↗
PubMed1988

Kinetics of drug action in disease states. XXIV. Pharmacodynamics of diazepam and its active metabolites in rats.

The purpose of this investigation was to determine the relative contribution of diazepam and its active metabolites (desmethyldiazepam, oxazepam and temazepam) to the hypnotic activity of this benzodiazepine drug and to assess the role of rate of drug administration as a determinant of the relative concentrations of diazepam and its active metabolites in serum and in the central nervous system at the onset of a predefined pharmacologic endpoint. Rats were given i.v. infusions of diazepam to onset of loss of righting reflex. Samples of cerebrospinal fluid (CSF), blood (for serum) and brain were obtained at that time and were analyzed for diazepam and its active metabolites. Based on the results of six experiments on groups of 6 to 14 rats performed at the same time of day over 11 months, the pharmacologic response of the animals was found to be relatively consistent, with little variation between rats and between experiments in body weight-normalized effective dose and in diazepam serum and CSF concentrations. All three active metabolites of diazepam were found in serum, CSF and brain; they were relatively more prominent in CSF than in serum. Variation of the diazepam infusion rate (four rates between 0.10 and 0.34 mg/min per approximately 200-g rat) was associated with changes in average onset time (50 to 10 min) and dose (26 to 17 mg/kg) required to produce the pharmacologic effect. The drug and metabolite concentrations in CSF determined in these experiments, together with corresponding concentrations obtained by infusion of each active metabolite individually, yielded estimates of their relative hypnotic potency that were unaffected by differences in serum protein binding and tissue distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The effect of diazepam on induction of anesthesia with alfentanil.

This study investigated the effect of intravenous diazepam on induction of anesthesia with alfentanil. Forty ASA physical status I and II patients were given one of four treatments: alfentanil 100 micrograms/kg or 200 micrograms/kg, without diazepam or preceded by 0.125 mg/kg diazepam intravenously. Blood pressure, heart rate, respiration, response to verbal command, and movement were assessed for 5 min, and blood was taken for measurement of histamine, epinephrine, and norepinephrine. All ten patients receiving 100 micrograms/kg and five of the ten patients receiving 200 micrograms/kg of alfentanil responded to voice after 5 min, but only one in each group responded when it was preceded by diazepam. There was no rigidity or serious arrhythmias in any patient. Heart rate increased in patients receiving alfentanil alone. Blood pressure increased in those receiving 100 micrograms/kg but not 200 micrograms/kg. In patients given diazepam, tachycardia did not occur, but blood pressure decreased after administration of alfentanil. There were no significant changes in plasma levels of histamine or catecholamines. Five of the six cases of inadequate postoperative ventilation were in patients given diazepam. Despite these effects, diazepam or some other hypnotic agent may be indicated when alfentanil is used for induction.

Adult↗
PubMed1988

Beta-carbolines as antagonists of the discriminative stimulus effects of diazepam in rats.

Rats were trained to discriminate between saline and 1.0 mg/kg of diazepam in a two-choice procedure where responding was maintained under a fixed-ratio, 5-response schedule of stimulus shock termination. beta-Carboline-3-carboxylate-methyl ester (beta CCM), beta-carboline-3-carboxylate-ethyl ester (beta CCE) and beta-carboline-3-carboxylate-t-butyl ester (beta CCtB), compounds with alkylcarboxy substitutions on the 3-position of the beta-carboline ring structure, were effective antagonists of the discriminative effects of diazepam. The 3-hydroxymethyl-substituted compound (3HMC) was relatively ineffective in antagonizing the discriminative effects of diazepam. The order of potency in antagonizing the 1.0 mg/kg training dose of diazepam was beta CCtB greater than beta CCM greater than beta CCE much greater than 3 HMC. The greater potency of beta CCtB likely reflects its resistance to metabolism in vivo. beta CCE and beta CCtB produced dose-related, parallel shifts in the dose-response curve for the discriminative effects of diazepam, but the magnitude of the shifts was limited: the two highest doses of beta CCE and beta CCtB produced shifts that were not significantly different in magnitude. These latter results suggest that these beta-carbolines antagonize only a portion of the component(s) of action of diazepam in producing discriminative stimuli. In contrast, the 7-substituted beta-carbolines harmane, harmol and harmine were ineffective in antagonizing the discriminative effects of diazepam up to doses of the beta-carbolines which disrupted the ability of the animals to respond.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Pharmacological analysis of chrono- and inotropic responses to diazepam in the isolated, blood-perfused canine atrium.

Effects of diazepam on the pacemaker activity and atrial contractility were investigated using the isolated and blood-perfused canine atrium. When diazepam in a dose range of 3-300 micrograms was injected directly into the sinus node artery, biphasic (negative followed by positive) chrono- and inotropic responses were dose-relatedly evoked. These responses were not affected by atropine in a dose which blocked ACh-induced negative ones. Propranolol inhibited positive chrono- and inotropic responses to diazepam, and prolonged the duration of the negative responses. Imipramine, in a dose which blocked tyramine-induced positive responses, significantly augmented the positive inotropic responses to diazepam. From these results, it is suggested that diazepam induces direct negative chrono- and inotropic effects, the mechanism of which remains to be defined, and indirect positive effects by catecholamine release from the sympathetic nerve terminals, though not mediated by a tyramine-like action. Diazepam tended to potentiate negative chrono- and inotropic effects of adenosine but not significantly, suggesting that diazepam plays a minor role as an adenosine potentiator in the dog right atrium.

Acetylcholine↗
PubMedDate not supplied

Recovery following sedation with midazolam or diazepam alone or in combination with fentanyl for outpatient surgery.

Midazolam is a new water-soluble benzodiazepine with a much shorter pharmacologic half-life than diazepam. Despite this shorter pharmacologic half-life, several reports indicate that patients do not recover more rapidly after sedation with midazolam than with diazepam. The purpose of this study was to compare recovery of patients sedated with either midazolam or diazepam alone or in combination with fentanyl using the digit symbol substitution test (DSST) and Trieger test. Patients were randomly divided into treatment groups and recovery tests were administered to the patients prior to sedation and at 60, 120, and 180 minutes after achieving a standardized sedative endpoint. Patients who received midazolam alone had significantly fewer numbers of correct reponses on the DSST than patients who received midazolam plus fentanyl or diazepam with or without fentanyl. When midazolam was combined with fentanyl there was no significant difference between results obtained on the DSST when compared with either diazepam group. Comparisons between all groups using dots missed or millimeter deviation on the Trieger test showed no statistical difference between any groups. These data indicate that midazolam as a single IV agent has a slightly prolonged recovery phase compared to diazepam. The addition of fentanyl to the sedation regimen allows reduction in the midazolam dose resulting in a recovery time comparable to that of diazepam.

Anesthesia Recovery Period↗
PubMed1987

Home cage pretreatment with diazepam: effects on subsequent conflict testing and rotorod assessment.

In various anxiolytic tests, benzodiazepines produce a maximal anxiolytic response only upon repeated treatment. The question arises as to whether repeated treatment produces an increase in anxiolytic efficacy or a decrease in another benzodiazepine-mediated effect (i.e., muscle relaxation/sedation) that functions to attenuate the full expression of the anxiolytic response. To address this issue, rats were pretreated in their home cages with either vehicle, diazepam or CGS 9896 (a nonsedating, non-muscle relaxant partial benzodiazepine agonist with anxiolytic efficacy) and challenged, 7 days later, with either diazepam or CGS 9896 in either a conflict (anxiolytic efficacy) or a rotorod (muscle relaxant/sedative effects) procedure. Rats who first experienced diazepam in the test situation (vehicle home cage pretreatment) showed only a moderate anxiolytic response and a compromised motor response. Pretreatment with diazepam in the home cage produced a tolerance to the motor-decreasing effects of diazepam and induced a maximal anxiolytic effect upon first challenge with diazepam in the test situation. CGS 9896, on the other hand, produced a maximal anxiolytic effect regardless of home cage pretreatment. Home cage pretreatment with CGS 9896 did not obviate the muscle relaxant/sedative or submaximal anxiolytic effects of diazepam, suggesting that repeated exposure to an anxiolytic effect is not the underlying basis for the repeated benzodiazepine treatment phenomenon. Rather, the motor-impairing effects of the benzodiazepines cause the submaximal response noted upon first exposure to these drugs in the anxiolytic test situation. This effect tolerates, leaving the expression of the maximal response.

Animals↗
PubMed1986

Neurotic depression accompanied by somatic symptoms: a double-blind comparison of flupenthixol and diazepam in general practice.

A total of 192 patients suffering from mild to moderate depression, with or without anxiety, accompanied by one or more specific somatic symptoms, was entered into a double-blind, multi-centre trial to compare flupenthixol and diazepam as treatments for psychosomatic syndromes in general practice. Each patient was treated for 4 weeks and assessed after 1, 2 and 4 weeks on the Hamilton Depression Scale, with visual analogue scales of depression and somatic symptoms, by global assessments (psychological and somatic symptoms) and on a side-effects scale. The principal somatic symptoms were tension headache (69 patients), epigastric discomfort (59 patients), chest pain (39 patients) and backache (25 patients). There were 9 drop-outs (2 on flupenthixol and 7 on diazepam), of whom 5 (2 on flupenthixol and 3 on diazepam) who were treated for at least 2 weeks were included in the analysis of results. All patients received 1 tablet a day (0.5 mg flupenthixol or 2.5 mg diazepam) for the first week. Thereafter, all except 5 patients (3 on flupenthixol and 2 on diazepam) had their dose doubled for the remaining 3 weeks of study. Both drugs were effective in producing consistent improvement in all four somatic symptom groups in terms of both depression and somatic symptoms over the 4 weeks of study. There was a trend throughout in favour of flupenthixol as the more therapeutically effective. Flupenthixol was significantly more effective in relieving depressive symptoms and somatic symptoms in all four somatic symptom groups considered together. It was also superior to diazepam as measured by its effect on the depression sub-scales, anxiety, agitated depression, retarded depression and melancholia. Both drugs were well tolerated, although diazepam-treated patients showed a moderate increase in side-effects scores initially, while the scores in patients treated with flupenthixol decreased consistently over all 4 weeks of the trial. It is concluded from this study that flupenthixol has an important place in the management of patients with psychosomatic illness.

Adult↗
PubMed1986

The influence of diazepam on the pharmacokinetics of intravenous and epidural bupivacaine in the rhesus monkey.

Pretreatment of patients with diazepam has been reported to reduce the plasma half-life of epidurally administered bupivacaine. The concentrations of bupivacaine used to estimate its plasma half-life may be influenced by input into the vascular system (rate and extent of absorption from the epidural space) and disposition (distribution and elimination). We conducted a study in Rhesus monkeys in which the input function was known and the influence of intravenous diazepam on the disposition of intravenous bupivacaine could be delineated. Results indicated no differences in the primary pharmacokinetic parameters (i.e., total clearance and volume of distribution) for the disposition of bupivacaine. To determine whether the apparent disparity between these results and a previous study might be due to a diazepam-induced alteration in the input function, the influence of intravenous diazepam or saline on the mean absorption time of epidurally administered bupivacaine was also studied in monkeys. Epidural bupivacaine was completely absorbed whether the animals received intravenous saline or intravenous diazepam. No significant differences in pharmacokinetic parameters were found between animals pretreated with intravenous saline or intravenous diazepam and receiving an epidural injection of bupivacaine. The mean residence time of bupivacaine in the body (P less than 0.01) and plasma elimination half-life (P less than 0.005) were significantly longer after epidural administration than after intravenous administration. Intravenous diazepam does not alter the pharmacokinetics of intravenously or epidurally administered bupivacaine.

Absorption↗
PubMed1985

Effect of halothane-oxygen anesthesia on the pharmacokinetics of diazepam and its metabolites in rats.

Inhalation anesthetics have been shown to substantially diminish the clearance of several drugs eliminated by hepatic routes. The purpose of the present study was to determine the influence of halothane-oxygen anesthesia on the hepatic metabolism of diazepam and its proximate metabolites in anesthetized rats whose physiologic status was monitored and maintained. The portal vein, femoral artery and bile duct of male Sprague-Dawley rats 370 to 395 g, were cannulated under pentobarbital anesthesia. After a 2-hr recovery period, [14C]diazepam was administered in to the portal vein as a 0.25-mg/kg bolus followed immediately by a 0.25-mg/kg/hr infusion by the same route. After the attainment of steady state, the halothane group (seven rats) received 1% halothane in oxygen whereas the control group (six rats) continued to breathe room air. The diazepam infusion was maintained for an additional 3 hr. Concentrations of diazepam, N-desmethyldiazepam, 4-hydroxyphenyldiazepam and 3-hydroxydiazepam were determined in plasma; these metabolites as well as oxazepam and N-desmethyl-4-hydroxyphenyldiazepam were also determined in bile. Radioactivity in bile was approximately 98% conjugated; radioactivity in plasma was approximately 30% conjugated. Halothane anesthesia caused an increase in the concentrations of diazepam and its metabolites in plasma, but the steady-state ratios of the concentration of the individual metabolites in plasma to diazepam concentration were not changed. The intrinsic clearance of diazepam was decreased by 42%, P less than .01, and the ratio of formation to elimination clearance of the metabolites measured in plasma was not changed. Halothane anesthesia also decreased the excretion rate of 14C into bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1985

Gender-related differences in diazepam effects on performance.

In order to investigate the possible differences of diazepam effects in the two sexes, two placebo-controlled double-blind studies were conducted on healthy volunteer students. In one study the subjects received diazepam 10 mg alone or combined with 0.5 g/kg of alcohol in a parallel group design; in the other 0.2 mg/kg of diazepam or placebo were given in a cross-over manner. In both trials diazepam impaired the psychomotor skills of women more than men. The difference was similar in tasks measuring cognitive (digit symbol substitution), motor (balance of extraocular muscles) and sensory (critical flicker fusion) performances. Tapping speed was affected to a similar degree in both genders. Diazepam 10 mg did not cause impairment of body balance, a parameter sensitive to alcohol. The combined effect of diazepam and alcohol was of similar magnitude in both sexes in all objective tests. Subjectively the women felt themselves clumsier than did the men. The calming effect was similar in both groups. The results suggest that while the performance of women may be more vulnerable than men to impairment by diazepam they also are aware of it. The difference of effects is of such magnitude that it may cause bias in experiments unless carefully balanced groups are used.

Adult↗
PubMed1975

Antiarrhythmic effects of diazepam during coronary artery occlusion in dogs.

The ventral interventricular branch of the left coronary artery was ligated in a 2-step operation in 10 dogs whose electrocardiograms and systemic arterial blood pressures were then monitored during the next 7 days. Monitoring was done in awake dogs given 1 mg of diazepam per kilogram of body weight (intravenously administered in 3 dogs and orally in 7). Because ventricualr ectopic activity was greatest during the interval of 10 to 48 hours after ligation, the antiarrhythmic activity of diazepam was recorded during this 38-hour interval. After administration of diazepam by either route, frequency of ventricular ectopic beats decreased from 98 to 80%. THIS REDUCTION BETAN IMMEDIATELY AFTER THE INTRAVENOUS ADMINISTRATION AND PERSISTED FOR ONLY 5 MINUTES; REDUCTION BEGAN APPROXIMATELY 1 HOUR AFTER THE ORAL ADMINISTRATION AND PERSISTED 4 TO 6 HOURS. Systemic arterial blood pressure decreased only after the intravenous administration. It is concluded that diazepam is effective in reducing the frequency of ventricular ectopic activity after occlusion of major branches of coronary arteries, that diazepam works independent of alterations in systemic arterial blood pressure, and that orally administered diazepam prolongs antiarrhythmic activity. Possibly, the adjuvants present in the parenteral form of diazepam reduce antiarrhythmic activity by being, themselves, arrhythmogenic.

Administration, Oral↗
PubMed1982

The involvement of monoaminergic and GABAergic systems in locomotor inhibition produced by clobazam and diazepam in rats.

The effects of 1,5-benzodiazepine clobazam and diazepam were evaluated with regard to behavioral locomotor changes in rats. A concurrent focus of investigation was whether or not both benzodiazepines interact with central monoaminergic and GABAergic mechanisms. Diazepam was more active than clobazam in reducing locomotor activity. The stimulation of locomotor activity induced by L-dopa plus benserazide, and methamphetamine was significantly counteracted by diazepam but unaffected by clobazam. Hypomotility produced by alpha-methyl-p-tyrosine was markedly augmented with both drugs. Locomotor suppression elicited by 5-HTP, activating central serotoninergic transmission, was more potently reversed by clobazam than by diazepam. In addition, arousal behavior produced by p-CPA, inactivating central serotoninergic transmission, was completely abolished by both drugs. Furthermore, in combination with AOAA, known to inhibit motor activity, diazepam had a synergistic effect, and picrotoxin-produced suppression was significantly antagonized by diazepam. Both benzodiazepines thus may exert their behavioral depressant effects by reducing catecholaminergic and serotoninergic activity, and also by promoting GABA-mediated inhibition in the central nervous system. Clobazam is more effective than diazepam in reducing serotoninergic activity, but less effective in reducing catecholaminergic activity and increasing GABAergic activity.

Animals↗
PubMed1983

Caffeine and theophylline counteract diazepam effects in man.

A total of 237 healthy subjects were studied in four placebo-controlled double-blind trials with parallel treatment groups. The subjects ingested a capsule (diazepam or placebo) and decaffeinated coffee with or without added caffeine or theophylline. Diazepam (10 and 20 mg) impaired dose dependently cognitive skills as measured by digit symbol substitution and letter cancellation, the balance of extraocular muscles, flicker fusion, and tapping speed. With diazepam 10 mg statistically significant effects were seen on digit symbols and exophoria only. Theophylline (10 mg/kg) increased tapping speed and heart rate, whereas other objective measurements were negative for the effects of theophylline or caffeine (250 and 500 mg) alone. Subjectively they reduced calmness, and caffeine also increased alertness. Caffeine 250 mg counteracted diazepam induced (10 mg) impairment of cognitive skills and relaxation of extraocular muscles whereas caffeine 500 mg counteracted the same effects of diazepam 20 mg, respectively. Theophylline antagonized diazepam-induced impairment in digit symbol substitution and tapping speed tests. Subjectively, caffeine and theophylline counteracted diazepam induced drowsiness and mental slowness. The results suggest, therefore, that the ample use of methylxanthines compensates various side-effects of benzodiazepines in man. It may also increase the need of sedation and thus the consumption of benzodiazepines.

Adult↗
PubMed1981

Differential inhibition by diazepam and nitrazepam of UDP-glucuronyltransferase activities in rats.

To assess the role of the N-alkyl group in the interaction of N-alkylated compounds on UDP-glucuronyltransferases, the effect of diazepam and nitrazepam, an N-desmethyl derivative of the diazepam class was studied on morphine, p-nitrophenol and testosterone glucuronidation in rats. Diazepam competitively inhibited the UDP-glucuroyltransferase activity for morphine in hepatic microsomes. The k value for morphine was 0.3 mM and the Ki for diazepam was about 0.23 mM. Also, diazepam administration to male rats reduced the glucuronyltransferase activity for morphine in rat hepatic microsomes in a dose effect relationship. Nitrazepam had no significant effect on morphine UDP-glucuronyltransferase activity in vitro or in in vivo experiments. Neither diazepam nor nitrazepam produced any effect on p-nitrophenol or testosterone glucuronidation in liver microsomal preparations. Single or repeated doses of these benzodiazepines did not change cytochrome P-450, RNA or protein contents of hepatic microsomes. It is suggested that morphine glucuronyltransferase contains an active site for binding of the N-methyl group present in the substrate. Such a binding site would be absent or in effective in p-nitrophenol and testosterone glucuronyltransferases. The reported inhibition of morphine metabolism by diazepam may account for an enhancement of morphine pharmacological effects.

Animals↗
PubMed1983

Absolute bioavailability of oral and intramuscular diazepam: effects of age and sex.

Twenty-two healthy volunteers aged 20-78 years received single 5-mg doses of diazepam by intravenous injection, by mouth in the fasting state, and by a deltoid intramuscular injection. The kinetic profile of diazepam by each route was determined from multiple plasma diazepam concentrations measured 7-14 days after each dose. After intravenous injection, diazepam volume of distribution (Vd) was larger in women than in men, but increased with age regardless of sex. Elimination half-life was longer in elderly than in young men (101 v 32 h, P less than 0.025), partly due to the increased Vd as well as to a significant reduction in total metabolic clearance (0.24 v 0.46 ml/min/kg, P less than 0.05). However, the prolonged half-life in elderly as opposed to young women (99 v 44 h; P less than .01) was due mainly to increased Vd because clearance was not significantly changed (0.29 v 0.35 ml/min/kg). In all subjects, oral diazepam was rapidly absorbed; peak plasma levels were reached an average of 0.9 h after dosage. Absolute bioavailability averaged 94%, indicating essentially complete absorption. Neither age nor sex significantly influenced oral absorption. In all male subjects, and in 8 of 12 women, absorption of diazepam after deltoid intramuscular injection was rapid and essentially complete. However, in three young and one elderly women, absorption was slower and apparently incomplete. Age as such did not significantly influence absorption of intramuscular diazepam.

Administration, Oral↗
PubMed1982

Stability of diazepam injection repackaged in glass unit-dose syringes.

The stability of diazepam injection repackaged in disposable glass syringes and stored at room and refrigerator temperatures was studied. Thirty-nine 1.5-ml syringes were filled with 1.1 ml diazepam injection 5-mg/ml. All syringes were stored in light-resistant bags on their sides so that the solution was in contact with the rubber stoppers on both ends. Samples were assayed with a stability-indicating HPLC method for diazepam and its degradation product, 2-methylamino-5-chloro-benzophenone (MACB), after 30, 60, and 90 days of storage at 30 degrees C and 4 degrees C. At 90 days, the diazepam injection stored at 4 degrees C retained 97.4 +/- 1.6% of its original potency; samples stored at 30 degrees C retained 92.4 +/- 1% of their original potency. Apparent sorption to rubber syringe components led to a decrease in the concentration of both diazepam and MACB. The decrease in diazepam was a function of storage time and temperature; however, the disappearance of MACB from the syringes was a function of only time. Diazepam injection is chemically stable as 5-mg doses in disposable glass syringes for 90 days when stored at 4 degrees C or 30 degrees C. However, refrigeration is recommended.

Diazepam↗
PubMed1980

Drug preference in humans: double-blind choice comparison of pentobarbital, diazepam and placebo.

In a residential hospital research ward setting the effects of and preference for placebo and various oral doses of pentobarbital and diazepam were studied in volunteer human subjects with documented histories of sedative abuse. Drug-free days alternated with drug administration days throughout the study. After experimenter-scheduled exposures to the test drugs, subjects were given repeated opportunities to choose between two available drug alternatives. In experiment 1, pentobarbital (200-900 mg) produced dose-related increases in subject- and observer-rated drug effects, and subjects generally chose higher pentobarbital doses over lower doses. In experiment 2, diazepam (50-400 mg) produced only modest elevations in drug effect ratings and subjects did not consistently choose higher doses over lower doses. In experiment 3, 400 mg of pentobarbital and 200 mg of diazepam produced subject and observer drug effect ratings of similar magnitude while placebo produced negligible effects. All subjects chose pentobarbital over placebo and diazepam over placebo on all occasions; all subjects chose pentobarbital over diazepam on the majority of choice trials. Clinical impression confirmed by a post hoc analysis of nursing notes indicated that diazepam produced relatively subtle yet reliable changes in the global mood and behavior of the subjects in the direction of increased complaining, dysphoria and disruptivenes. The finding that pentobarbital is preferred to diazepam is compatible with previous human and animal drug self-administration studies as well as clinical information about the abuse of these drugs.

Adult↗