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At least 19 recordsLinked to original sources
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↗
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↗
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↗
PubMed1978

Experimental barbiturate dependence. I. Barbiturate dependence development in rats by drug-admixed food (DAF) method.

A method for testing a rat's physical-dependence liability to sedaditive-hypnotic agents and for evaluating that dependence was studied by using the method. Rats received phenobarbital- or barbital-admixed food on a graded-increase dosage schedule over 30-40 days. Manifestations of CNS-suppressing action of either drug (e.g., systemic muscle relaxation, motor incoordination, staggering gait, and ptosis) persisted day and night during the drug medication. Twenty-four to 48 h after withdrawal of either drug, abstinence symptoms (e.g., muscle fasciculation, nuchal twitching, vocalization, increased irritability, ataxia, hyperthermia, and clonic-tonic and grand mal-type convulsions) were evidenced in all animals (N = 6), some of which died after convulsions. These withdrawal signs in rats were classified and found to be closely correlated with the magnitude of weight loss during the withdrawal. The calssification provides a basis for quantitatively assessing physical-dependence liability. The data obtained in the present study suggest that rats, like dogs and monkeys, are suitable experimental animals for tests in early stages of dependence liability, and that the administration of drug-admixed food is a useful method of developing dependence on both barbiturate and morphine-type drugs.

Animal Feed↗
PubMed1975

Interactions of tricyclic antidepressants and barbiturates in barbiturate-tolerant and nontolerant rats.

Pretreatment of rats with tricyclic antidepressants, imipramine, desipramine, amitriptyline and nortriptyline, at two doses (5 and 25 mg/kg) 20 minutes before administration of barbiturate markedly reduced the latent period of the response to barbital and prolonged the sleeping time induced by pentobarbital (PB) and barbital. The effects were dose-dependent. The prolonged sleeping time produced by PB was associated with decreases in the rates of disappearance of PB from the brain and plasma. The effect of tricyclic antidepressants on PB hypnosis in PB-tolerant and nontolerant rats was apparently not related to change in central nervous system (CNS) sensitivity to PB, since at the time of awakening there were no significant differences in the concentrations of unmetabolized PB in either the plasma or brain of tricyclic antidepressant-treated animals as compared to controls. As barbital is not metabolized, potentiation of barbital hypnosis by tricyclic antidepressants must be attributable to a direct effect on CNS rather than on liver microsomal enzymes. Direct evidence was provided by the findings that amitriptyline accelerated the brain uptake of barbital and that amitriptyline-treated animals lost and recovered the righting reflex at brain barbital levels lower than those of controls. Rats made tolerant to the hypnotic effect of barbital also became tolerant, in varying degrees, to the hyposis-prolonging properties of tricyclic antidepressants. It is concluded that tricyclic antidepressants prolong PB sleeping time in PB-tolerant and nontolerant rats by inhibiting its biotransformation in the liver. The action of tricyclic antidepressants to prolong the hypnotic action of barbital in normal rats is related to their direct effects on CNS sensitivity to barbital, but such effects are makedly diminished after animals become tolerant to barbital.

Amitriptyline↗
PubMed1988

Photochemical degradation of barbituric acid derivatives. Part 8: Photolysis of sodium salts of barbiturates in solid state.

After the UV irradiation of suspensions of barbiturate sodium salts in paraffin oil the IR spectra revealed two IR absorption bands at ca. 2170 and 2250 cm-1. The effects of different conditions of the photochemical process and the addition of nucleophilic reagents after irradiation on the intensity of these bands were studied. The origin of 2170 cm-1 band was interpreted in terms of the isocyanate intermediate which is formed after the pyrimidine ring opening.

Barbiturates↗