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At least 19 recordsLinked to original sources
PubMed1984

Reflex sympathetic dystrophy syndrome and barbiturates. A study of 25 cases treated with barbiturates compared with 124 cases treated without barbiturates.

Amongst 149 cases of reflex sympathetic dystrophy syndrome (RSDS), 25 (16.8%) were being treated with barbiturates at the time the RSDS symptoms began. This group is unusual by the frequent absence of provocative events (32%), a high number of diseased joints, bilaterality (76%), involvement of upper limbs (76%) and Dupuytren's disease (52%). Swift and complete recovery depends mostly on barbiturate withdrawal. These data support the idea that barbiturates may be the principal initiating event in some RSDS. Since unfavorable progress is seen with persistent use of barbiturates, this medication should be recognised early in the course of the disease in order to prevent severe sequels.

Adult↗
PubMed1959

A barbiturate antidote. Use of methylethyl-glutarmide in barbiturate intoxication and in terminating barbiturate anesthesia.

Methylethylglutarimide was administered to 488 patients ranging in age from 7 to 89 years, in a study on sleep-reversal after harbiturate anesthesia. Sodium surital or sodium pentothal were the barbiturates used. The drug was administered intravenously in doses varying from 25 to 200 mg. Dosage below 25 mg. was found to be ineffective. Almost all patients showed signs of awakening as evidenced by the return of corneal and conjunctival reflexes, the opening of the eyes, and stirring or moving about. Many responded to questioning. Almost all showed evidence of greater responsiveness within five minutes. No untoward reactions were noted. No convulsions were produced. Five patients ranging in age from 24 to 70 years were treated for barbiturate poisoning with Mikedimide(R) given intravenously in doses varying from 550 mg. to 1950 mg. All recovered consciousness within 30 minutes to an hour. No convulsions were produced. While it is not known whether Mikedimide is a direct barbiturate antagonist, or whether it is an analeptic, it appears to be a useful drug in reversing the respiratory depression and the cerebral depression produced by harbiturate intoxication and barbiturate anesthesia.

Anesthesia↗
PubMed1982

Barbiturate inhibition of lymphocyte function. Differing effects of various barbiturates used to induce coma.

The present studies evaluated the effect of phenobarbital, pentobarbital, and thiopental at concentrations comparable to those attained during therapeutic barbiturate-induced coma, on in vitro mitogen-induced lymphocyte activation. Lymphocytes from normal volunteers were incubated for 72 hours in culture medium containing mitogen (phytohemagglutinin) and a range of concentrations of the barbiturates (5 to 833 microgram/ml). Three parameters of lymphocyte activation (mitogen-induced blast transformation, 3H-thymidine incorporation, and cell proliferation) were all suppressed by the barbiturates. The suppression was dose-dependent. The greatest suppression was caused by the short-acting barbiturate, thiopental. Lymphocyte responses were much less affected by the long-acting barbiturate, phenobarbital. The intermediate-acting barbiturate, pentobarbital, was also intermediate in its ability to inhibit lymphocyte activation. The two-to threefold difference between the effects of thiopental and pentobarbital on lymphocyte function may have direct clinical relevance, since it is primarily these two agents that are employed to induce therapeutic "barbiturate coma." Since lymphocyte suppression appears to be much more marked in the presence of thiopental, these observations support a role for the other barbiturates in programs of induced coma.

Barbiturates↗
PubMed1965

Barbiturate mortality as an index barbiturate use, Canada, 1950-1963.

Changes in Canadian rates of mortality from barbiturates are examined, and their relation to barbiturate use in the general population is discussed. While the number of deaths attributed to barbiturates quadrupled, from 63 in 1950 to 232 in 1963, there has been a concomitant decrease in the number of deaths from inhalation of utility gas.Combined rates for deaths from utility gas and barbiturates declined steadily for most age groups between 1950-52, 1955-57, and 1959-63. It is possible that the increased mortality from barbiturates represents a change in fashion in regard to method of suicide. Changed mortality from barbiturates is not a valid measure of the extent to which consumption of barbiturates has increased in the Canadian population.

Adolescent↗
PubMed1970

Barbiturate blood levels found at necropsy in proven cases of acute barbiturate poisoning.

In order to determine whether blood barbiturate levels could be used to ascertain that death had been caused by barbiturate overdose, samples of blood from 128 subjects of coroners' necropsies were examined for barbiturate content. Sixty of these were well authenticated cases of barbiturate overdosage, and barbiturates were implicated, together with other factors such as alcohol and carbon monoxide, in a further 16 cases. The remaining 52 cases were of an eliminatory nature, 10 of which had low barbiturate blood levels considered to be within the therapeutic range.The results indicate that when the accepted levels producing loss of consciousness are exceeded, and maintained, death will ensue if treatment is not given. These results may be of value in assessing findings in necropsies requested by the coroner, and are in no way applicable to the living patient in whom it is well established that recovery from higher blood levels may take place if adequate treatment is available.

Amobarbital↗
PubMed1975

Radioimmunoassay of drugs subject to abuse: critical evaluation of urinary morphine-barbiturate, morphine, barbiturate, and amphetamine assays.

Radioimmunoassays for morphine-barbiturate (MOR-BARB), morphine, barbiturate, and amphetamine were evaluated by a direct comparison with differential elution extraction thin-layer chromatography, the "enzyme multiplied immunoassay technique," and XAD-2 resin extraction thin-layer chromatography for the detection in urine of drugs subject to abuse. Statistically significant (Psmaller than 0.01) concentrations for detection were: 50-100 mug/liter for MOR-BARB; 5 Mug/liter for morphine, 10 mug/liter for barbiturate, and 100 mug/liter for amphetamine. Unconfirmed and unaccounted-for radioimmunoassay positives (false) were: 0% for morphine in the radioimmunoassay for MOR-BARB and that for morphine alone; 2.8% for barbiturates in the MOR-BARB assay and that for barbiturates alone; 0-6% when a combination of these drugs was present in the MOR-BARB, morphine, or barbiturate assay; and 2.4% in the amphetamine radioimmunoassay. Less than 1% of all radioimmunoassay-negative samples were unconfirmed (false). Cross-reactivity was observed with drugs of a similar chemical structure in each of the radioimmunoassays tested. All the radio-immunoassays were easy to use, highly sensitive, and extremely reliable for detecting drug use or abuse.

Amphetamine↗
PubMed1984

[Significance of prolonged barbiturate therapy on severe head injuries--ICP regulation and duration of barbiturate administration].

Barbiturate therapy was performed on 84 head trauma patients which were measured on GCS score of 8 or less, through October 1979 to December 1982. More than 3 g/day of thiamylal or more than 1.5 g/day of pentobarbital were administered for barbiturate therapy. Barbiturate therapy was discontinued in patients whose ICP remained less than 20 mmHg for more than 36 hours. In patients whose ICP sustained higher level, barbiturate was administered continuously until brain death was confirmed or non-filling was recognized. The patients were divided into two groups; Group I in which barbiturate therapy was carried out for 72 hours or less, and Group II in which it was administered for more than 72 hours. The patients in each group were further divided into responder and survivor (a), responder but late death (b), and no-responder or acute brain death (c), As far as age of patients concern, 19 out of 26 patients whose age was less than 20, 22 out of 35 patients whose age was 20-50 and 13 out of 23 patients whose age was more than 50 years responded well to the barbiturate therapy. But one patient died among young age, 4 patients died among middle age and 9 patients died among aged group at later stage. As for Group I (51 patients), Group I a consisted of 22 patients (mean age; 26.2 years, mean GCS score; 6.04, mean initial and maximal ICP; 11.9 and 27.8 mmHg), I b of 8 (52.5 years, 4.75, 17.0 and 27.8 mmHg), and I c of 21 (41.4 years, 4.57, 38.1 and 98.0 mmHg respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1982

Studies on the interaction of barbiturates with reactive oxygen radicals: implications regarding barbiturate protection against cerebral ischaemia.

Although the molecular basis of ischaemic damage of the brain is as yet unknown, it has been postulated that the uncontrolled production of reactive oxygenated species derived from molecular oxygen (including hydroxyl radicals, superoxide radicals and singlet oxygen) may play a major role in the production of such injury. The ability of various barbiturates to modify the nature and extent of membrane damage produced by various oxygen radicals generated under well-defined conditions in vitro has been directly examined using the human erythrocyte as model membrane system. Our results indicate that barbiturates are unlikely to exert their protective effects by directly scavenging singlet oxygen, superoxide or hydroxyl radicals. The highly lipophilic barbiturate thiopentone is capable of decreasing the susceptibility of membranes to oxidative degradation by a direct membrane action, a property shared by amphipathic membrane stabilizers such as propranolol. The barbiturates were found to stabilize the haeme moiety of haemoglobin preventing its conversion to methaemoglobin in the presence of hydrogen peroxide. It is postulated that a major aspect of barbiturate action in decreasing ischaemic injury to the brain may involve the stabilization of haeme-coordinated iron complexes, thereby preventing the participation of these ubiquitous substances in initiating and potentiating free radical-mediated processes which have been implicated in the production of such injury.

Barbiturates↗
PubMedDate not supplied

Quantitation of barbiturates by a modification of the EMIT-tox serum barbiturate assay.

A modification of the Syva EMIT-tox Serum Barbiturate Assay was developed to provide a rapid and practical method for quantitating serum barbiturates. Standard curves for eight selected barbiturates were run using specific sets of standards for each. Correlation coefficients, slopes, and y-intercepts for the curves of best fit were determined by the least-squares method. Between-run and within-run precision analysis indicated acceptable reproducibility for barbiturate concentrations in high therapeutic to toxic serum levels. A case report describing the use of this method for the determination of serum pentobarbital concentrations during therapy for intracranial hypertension is presented. The modified EMIT assay may be useful for monitoring barbiturate blood levels in overdose, and when used for therapy of ischemic brain damage.

Antibody Specificity↗
PubMed1983

Induction by barbiturates of a cytochrome P-450-dependent fatty acid monooxygenase in Bacillus megaterium: relationship between barbiturate structure and inducer activity.

In a recent communication (Narhi, L. and Fulco, A.J. [1982] J. Biol. Chem. 257, 2147-2150) we found that a soluble cytochrome P-450-dependent fatty acid monooxygenase isolated from Bacillus megaterium ATCC 14581 could be induced about 28-fold by phenobarbital. We have now examined 19 barbiturates and found that 13 significantly induce the specific monooxygenase activity. Of these, 11 are more active than phenobarbital and three (secobarbital, thiamylal and methohexital) are more than 30 times as active on a molar basis. The dialkyl barbiturates without exception show an excellent correlation between increasing lipophilicity and increasing potency as inducers as do most of the barbiturates containing an aromatic substituent. Nevertheless, it is apparent that certain structural features involving factors other than lipophilicity are also necessary for induction. Our finding that barbiturates can cause the non-substrate induction of a cytochrome P-450-dependent monooxygenase in a prokaryote represents a unique discovery that may provide a relatively simple model for apparently similar induction systems in higher animals.

Bacillus megaterium↗
PubMed1983

Reactivity of EMIT serum barbiturate assay reagents: potential application for the quantitation of selected barbiturates.

The reactivity of EMIT serum barbiturate assay reagents toward barbiturate test compounds was investigated. Reactivity was determined by the C5 substituents on the barbiturate ring and O/S substitution (barbituric/thiobarbituric acid derivatives). Reagents were more reactive toward a 5,5-substituted barbiturate than toward its hydroxylated analogue. EMIT reactivity could be linearized vs. concentration of test compound, allowing for quantitative analysis in serum or plasma.

Barbiturates↗
PubMed2005

[Studies on the structure-activity relationship of allyl substituted oxopyrimidines searching for the novel antagonist or agonist of barbiturates to the sleep mechanism based on the uridine receptor theory--barbituric acid to uridine (part I)].

Thirty-six allyl substituted oxopyrimidine analogues such as barbituric acid (BA), barbiturates, uracil, thymine, and related derivatives including 13 new compounds were synthesized and their pharmacologic effects ([hypnotic activity, anticonvulsant activity against pentylentetrazol (PTZ)-induced seizures, and LD(50)]) and interactions with the barbiturates were evaluated in mice and rats. The results are briefly and parially summarized as follows. BA prolonged pentobarbital (PB)-induced sleep and had some central depressant effects. N,5,5-triallyl-BA exhibited some hypnotic and anticonvulsant activities, although the other 5,N-allyl-compounds did not show any activity except for allobarbital (AlloB). N-allyl-BA, 5-allyl-BA, N(1),N(3),5-triallyl-BA, N,5,5-triallyl-BA, and N(1),N(3),5,5-tetraallyl-BA also prolonged PB-induced sleep. Interestingly, N,5,5-triallyl-BA was the most potent in the interaction with AlloB, phenobarbital (PheB), amobarbital (AB), PB, and thiopental (TP) but not barbital (B). N(1),N(3),5,5-tetraallyl-BA prolonged AlloB-, PB-, and AB-induced sleep but not B-, PheB-, and TP-induced sleep. N(1),N(3),5-triallyl-B prolonged only PB- and TP-induced sleep. 5,5-diallyl-BA prolonged PheB- and TP-induced sleep. N,5-diallyl-BA prolonged only TP-induced sleep. In contrast, BA and N(1),N(3),5-triallyl-AB tended to antagonize AlloB, AB, and B. N(1),N(3),5,5-tetraallyl-BA also slightly antagonized B, PheB, and TP. 5,5-diallyl-BA antagonized only AB. The prolonging effects of BA, N,5,5-triallyl-BA, and N(1),N(3),5,5-tetraallyl-BA on PB-induced sleep were dose dependent. These results indicate that the position and number of allyl groups substituted on the structure of BA play an important role in their depressant activities. This review deals with the structure-activity relationship of allyl-substituted oxopyrimidines as part of our search for antagonists and agonists of barbiturates as well as their mechanisms of action.

Animals↗
PubMed1987

[No indications for barbiturate therapy following complete cerebral ischemia. A comment on "cerebroprotection" by barbiturates following cardiovascular arrest].

Cardiac arrest is followed by complete cerebral ischemia, which is characterized by delayed hypoperfusion and transient hypermetabolism. Brain metabolism depressant drugs, such as barbiturates, were suggested to improve neuronal outcome. The hypothesis of a cerebroprotective effect of barbiturates remained nevertheless controversial. In order to define the utility of large doses of thiopentone, the effect of thiopentone on carbohydrate and energy metabolism of 1-year old Wistar rats was investigated in an experimental model of complete reversible ischemia followed by a recovery period. No beneficial effect of high-dose thiopentone could be demonstrated by means of changes in the carbohydrate metabolism and the energyrich compounds. There were no differences between the treated group and the spontaneous recovery group. These results are mainly confirmed by other investigators. In contrast to focal ischemia and hypoxemia beneficial effects of barbiturates can not be demonstrated after complete cerebral ischemia in experimental studies and in clinical studies as well. In conclusion there is no indication for high-dose barbiturate therapy after cardiac arrest and successfull resuscitation.

Animals↗
PubMed1993

Inhibition by barbiturates of the binding of Bm3R1 repressor to its operator site on the barbiturate-inducible cytochrome P450BM-3 gene of Bacillus megaterium.

In our previous publication (Shaw, G.-C., and Fulco, A. J. (1992) J. Biol. Chem. 267, 5515-5526), we reported that Bm3R1, a protein encoded in an open reading frame just upstream from the cytochrome P450BM-3 gene, is a repressor critically involved in the barbiturate-inducible expression of this gene in Bacillus megaterium. We now describe the purification of the Bm3R1 protein from an overproducing Escherichia coli strain harboring a bm3R1 gene-carrying plasmid and report the effect of barbiturate inducers on the interaction of Bm3R1 with a fragment of B. megaterium DNA containing the bicistronic operator and promoter sequences. Gel filtration analysis revealed that, under our experimental conditions, most of the Bm3R1 protein exists in highly aggregated forms. Gel mobility shift assays showed that Bm3R1 protein bound specifically to a segment of DNA containing the promoter-operator region of the bm3R1 gene while DNase I footprinting experiments established that Bm3R1 protected a region of DNA that covers and flanks the palindromic operator sequence. The interaction between Bm3R1 repressor and its operator, in vitro, was strongly inhibited by the addition of 2 mM pentobarbital or 2 mM methohexital (strong in vivo inducers of P450BM-3) but not by the same concentration of phenobarbital (a relatively weak inducer) or by mephobarbital (a non-inducer). A detailed comparison of pentobarbital and methohexital at concentrations lower than 2 mM indicated that methohexital was 5-10 times more effective as an inhibitor of Bm3R1 binding in vitro, as compared with its 7-fold greater inducer potency in vivo. The observation that the in vitro inhibition effects of barbiturates on the interaction of Bm3R1 repressor and its operator correlate strongly with their in vivo potency as inducers of cytochrome P450BM-3 suggests a mechanism for the induction process. It seems plausible that the barbiturate inducers might bear a conformational resemblance to and mimic the mode of action of an as yet unidentified endogenous inducer(s) in B. megaterium that functions by releasing the binding of Bm3R1 repressor from its operator site.

Bacillus megaterium↗
PubMed1979

Convulsant, anticonvulsant and anaesthetic barbiturates. 5-Ethyl-5-(3'-methyl-but-2'-enyl)-barbituric acid and related compounds.

Barbiturates derived by minor structural changes to the butenyl sidechain of the convulsant 5-ethyl-5-(3'-methyl-but-2'-enyl)-barbituric acid are almost devoid of convulsant activity, but all have anaesthetic and anticonvulsant effects. Anticonvulsant activity is also observed in the convulsant barbiturate. Increased lipophilic character does not increase anaesthetic potency, only speed of onset, and anticonvulsant activity is reduced in the more lipophilic compounds. The stereochemistry at the 3'-position of the sidechain is vitally important to convulsant activity, and also influences anticonvulsant potency.

Anesthetics↗
PubMed1978

Glass formation in barbiturates and solid dispersion systems of barbiturates with citric acid.

Glasses were prepared from a number of barbiturates. The viscosities and glass transition temperatures of the glasses were dependent on the structure of the groups present on the C-5 and N-1 atoms. Solid dispersions were prepared from three selected barbiturates formulated with citric acid. The glass transition temperatures of these systems indicated that a 1:1 molar ratio complex was formed between the two components and that intermolecular bonding was stronger in the complex than in the individual components.

Barbiturates↗
PubMed1987

GABA-ergic mechanisms in the anticonvulsive activity of newly-synthesized barbiturates. I. Effects of barbiturates on the convulsive action of GABA-antagonists.

The anticonvulsive activity of seven newly-synthesized derivatives of barbituric acid, having a hydroxylamins groups substituted in second position, with respect to convulsive agents related with the GABA-ergic transmitter system: picrotoxin, bicuculline, thiosemicarbazide and 3-mercaptopropionic acid, was studied in experiments on mice. The anticonvulsive activity of these compounds in allylglycine-induced convulsions was investigated in experiments on rats, and was compared to that of well-known drugs, such as pentobarbital, phenobarbital, allobarbital and diphenylhydantoin. The results obtained show that the hydroxylamine derivatives of barbituric acid HB-2 (2-hydroxylamino-5-ethyl-5-propylbarbituric acid) and HB-7 (2-hydroxylamino-5-ethyl-5 sec. pentylbarbituric acid) have the most pronounced anticonvulsive activity, which suggests the considerable importance of the participation of GABA-ergic transmission in the realization of this activity.

3-Mercaptopropionic Acid↗
PubMed1991

Drastic changes of ventromedial medulla neuronal properties induced by barbiturate anesthesia. II. Modifications of the single-unit activity produced by Brevital, a short-acting barbiturate in the awake, freely moving rat.

In the preceding study, we have found that pentobarbital, a powerful barbiturate substance, strongly modified the ventromedial medulla (VMM) physiology in relation to nociception: indeed, in the same rats, during time-separated similar VMM penetrations, we have recorded, under pentobarbital, 'new' neuronal groups as compared to the awake state, such as the units exclusively driven (excited or inhibited) by cutaneous innocuous or noxious stimulations and the multimodal multireceptive neurons inhibited by non-noxious and noxious stimuli. Still under pentobarbital, we have also recorded the same units found as the rats were awake, i.e., the multimodal multireceptive neurons exclusively excited by various innocuous and noxious stimuli. However, the spontaneous and nociceptive activities of these units were strongly modified as compared to awake animals. Using Brevital (a short-acting barbiturate substance) administration, we have, in the present study, tried to understand the mechanisms underlying these drastic modifications. In particular, one of the questions was whether or not the 'new' neuronal classes recorded under anesthesia resulted from a modification of the physiological properties of the unique VMM neuronal group potentially involved in nociception in awake animals: the multimodal multireceptive units. By following the VMM neuronal activities either before and after or after Brevital administration until recovery from anesthesia, we have determined that the units exclusively driven by innocuous stimulation might result from a modification of the multimodal multireceptive neurons. Alternatively, the multireceptive units inhibited by peripheral stimulations are possibly totally different neurons, silent when the animals are awake.

Anesthesia↗