Barbiturates bromide

The treatment of anxiety throughout human history has involved a variety of natural agents which were administered to relieve tension and induce a state of altered consciousness, with ethanol in its various forms the most widely used [4]. Within the last century, general CNS depressants such as barbiturates, bromide salts, and ethanol surrogates such as chloral hydrate and paraldehyde have been employed to treat anxiety. Because of side-effects of the other drugs, barbiturates were used predominantly in the first half of this century as anxiolytics, but their clinical utility was limited by tolerance and dependence liability. Propanediolcarbamates such as meprobamate were also used to treat anxiety but displayed many of the barbiturate side-effects. 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

An early application of this reaction to the preparation of barbiturates starts by the condensation of the ketone, I21, with ethyl cyanoacetate by Knoevenagel condensation. Alkylation of the product (122) with ethyl bromide by means of sodium ethoxide affords 123. Condensation of this intermediate with guanidine in the presence of sodium ethoxide gives the diimino analog of a barbiturate (124). Hydrolysis affords vinbarbital (111). > ... 

Cyclization of the two pendant alkyl side chains on barbiturates to form a spiran is consistent with sedative-hypnotic activity. The synthesis of this most complex barbiturate starts by alkylation of ethyl acetoacetate with 2-chloropentan-3-one to give 152. Hydrolysis and decarboxylation under acidic conditions gives the diketone, 153. This intermediate is then reduced to the diol (154), and that is converted to the dibromide (155) by means of hydrogen bromide. Double Internal alkylation of ethyl... 

Propyl-methyl-carbiny I barbituric acid Allyl bromide Sodium hydroxide... 

Propyl-methyl-carbinyl allyl barbituric acid (also called allyl 1-methyl-butyl barbituric acid) may be prepared as follows 1 mol of propyl-methyl-carbinyl barbituric acid is dissolved in a suitable vessel In a 10 to 35% aqueous solution of 1 mol of potassium hydroxide. To this are added somewhat in excess of 1 mol of allyl bromide, and alcohol equal to about 10% of the total volume of the solution. The vessel Is agitated for 50 to 75 hours. At the end of this time, the solution, which may still exhibit two layers, is concentrated to about one-half its volume to remove the excess allyl bromide and the alcohol. On cooling, an oily layer, which is propyl-methyl-carbinyl allyl barbituric acid, separates out as a sticky viscous mass. It is dried, washed with petroleum ether, and dissolved in the minimum amount of benzene. Any unreacted propyl-methyl-carbinyl barbituric acid, which does not dissolve, is filtered off. The addition of petroleum ether to the clear filtrate causes the propyl-methyl-carbinyl allyl barbituric acid to precipitate as an oily mass. 

Other methods for the determination of chlorine in seawater or saline waters are based on the use of barbituric acid [13] and on the use of residual chlorine electrodes [ 14] or amperometric membrane probes [15,16]. In the barbituric acid method [12], chlorine reacts rapidly in the presence of bromide and has completely disappeared after 1 minute. This result, which was verified in the range pH 7.5-9.4, proves the absence of free chlorine in seawater. A study of the colorimetric deterioration of free halogens by the diethylparaphenylene-diamine technique shows that the titration curve of the compound obtained is more like the bromine curve than that of chlorine. The author suggests... 

It is interesting to note that one of the founders of modern psychiatry, Kraepelin, listed only nine substances that were available for the treatment of psychiatric illness in the 1890s. These were opium, morphine, scopolamine, hashish, chloral hydrate, a barbiturate, alcohol, chloroform and various bromides. Later Bleuler, another founder of modern psychiatry, added paraldehyde and sodium barbitone to the list. Thus psychopharmacology is a very recent area of medicine which largely arose from the chance discovery of chlorpromazine by Delay and Deniker in France in 1952, and of imipramine by Kuhn in Switzerland in 1957. 

Carbromal (Uradal, Adalin.) 1 mole of a-bromo-a-ethyl butyryl bromide is mixed with dry urea (1 mole) and heated on a steam bath for several hours. Precautions must be taken to keep steam and atmospheric H2O from the reaction vessel. Cool, allow to solidify, wash with H2O, and recrystallize from alcohol. Dose (sedative) 300 to 500 mg, (hypnotic) 700 to 950 mg, mp 116-118°. This drug is less potent than the barbiturates, but it is less toxic, extremely well tolerated, has a wide margin of safety, and acts rapidly. 

The first effective treatment of seizure disorders was the serendipitous finding in 1857 that potassium bromide could control seizures in some patients. Even though side effects were troublesome, the bromides were widely used for many years. Phenobarbital was introduced as a treatment for epilepsy in 1912 and was immediately shown to be markedly superior to bromides. While other barbiturates were synthesized and used, none were shown to be superior to phenobarbital, and the latter compound is still used. A chemically related... 

Long introduces ether as an anesthetic Locock accidentally discovers bromides as anticonvulsants Lister pioneers use of phenol as a surgical antiseptic Liebreich discovers hypnotic effects of chloral hydrate Strieker uncovers analgesic properties of salicylic acid Guthzeit and Conrad synthesize a series of barbiturates Erlich pioneers concepts of receptor and chemotherapy ... 

Humanity s centuries-old, avid search for substances that would relieve these conditions has resulted in a progression from alcohol to opiates to the synthesis of bromides and barbiturates. Each of these, however, shares treatment-limiting and potentially life-threatening disadvantages, including the following ... 

Aside from the bromides, phenobarbital is the oldest of the currently available antiseizure drugs. Although it has long been considered one of the safest of the antiseizure agents, the use of other medications with lesser sedative effects has been urged. Many consider the barbiturates the drugs of choice for seizures only in infants. 

There is a very great demand for drugs for the relief of anxiety. This was formerly met by the use of alcohol, bromides or barbiturates, which carried the risk of abuse or dangerous toxicity. The first of the modern minor tranquilizers, introduced from 1946 onwards, were drugs described as skeletal muscle relaxants. These were mainly derivatives of polyhydric alcohols, but heterocyclic examples included metaxolone (161), which is related to the aryl ethers of glycerol, chlorzoxazone (162) and chlormezanone (163). Dantrolene sodium (164) is a muscle relaxant and CNS depressant. 

Barbiturates (a class of drugs with more effective sedative-hypnotic effects) replace most use of sedative bromides. 

Barbiturates (a class of drugs with more effective sedative-hypnotic effects) replaced bromides in 1903. Depending on the dose, frequency, and duration of use, however, tolerance, physical dependence, and psychological dependence on barbiturates can occur relatively rapidly. With the development of tolerance, the margin of safety between the effective dose and the lethal dose becomes very narrow. That is, in order to obtain the same level of intoxication, the tolerant abuser may raise his or her dose to a level that can produce coma and death. 

Historically the first sedative hypnotics to be introduced were the bromides in the mid 19th century, shortly followed by chloral hydrate, paraldehyde and urethane. It was not until the early years of this century that the first barbiturate, sodium barbitone, was developed and this was shortly followed by over 50 analogues, all with essentially similar pharmacological properties. The major breakthrough in the development of selective, relatively non-toxic sedative hypnotics followed the introduction of chlordiazepoxide in 1961. Most of the benzodiazepines in current use have been selected for their high anxiolytic potency relative to their central depressant effects. Because of their considerable safety, the benzodiazepines have now largely replaced the barbiturates and the alcohols, such as chloral hydrate and trichloroethanol, as the drugs of choice in the treatment of insomnia. 

Allyl bromide Propyl-methyl-carbinyl barbituric acid... 

Propyl-methyl-carbinyl allyl barbituric acid (also called allyl 1-methyl-butyl barbituric acid) may be prepared as follows 1 mol of propyl-methyl-carbinyl barbituric acid is dissolved in a suitable vessel in a 10 to 35% aqueous solution of 1 mol of potassium hydroxide. To this are added somewhat in excess of 1 mol of allyl bromide, and alcohol equal to about 10% of the total... 

The researchers Joseph von Mering and Emil Fischer, a student of von Baeyer, developed the first barbiturate drug to be marketed. Fischer produced 5.5-diethylbarbituric acid, a hypnotic (medication to help patients sleep) and sedative (medication to relax people with constant nervousness and anxiety). This sedative/hypnotic drug was known by the trade names Barbital, Veronal, and Dorminal. Barbital proved to be a more effective sedative/hypnotic agent and replaced the class of drugs, sedative bromides, which were used at the time.14... 

Barbiturates are used not only to treat human seizures. Pheno-barbital is the most common medication used to treat seizures in pets, like dogs. Generally if pets have more than one seizure every one or two months they may need a medicine for seizure prevention, although a veterinarian should decide if one is necessary. Phenobarbital may be used alone or in combination with potassium bromide, a very old seizure medicine for humans. Like people, some young pets may grow out of their seizures as they mature.19... 

Pentozocine Lactate Injections of pentozocine lactate are incompatible with sodium bicarbonate, barbiturates, diazepam, chlordiazepoxide, glycopyrronium bromide, and nafcillin sodium. Dependence, withdrawal, and treatment of adverse effects are generally similar to those of opioid analgesics. 

Magnesium, 12, 48 Malononitrile, 10, 66 Malonylurea, see Barbituric acid Mercuration, 12, 46, 54 Mercuric chloride, 12, 54 Mercuric oxide, 12, 44 Mercury di-/3-naphthyl, 12, 46 Mesaconic acid, 11, 74 Mcsitylene, 11, 24, 67 Methylamine, 12, 38 Methylamine hydrochloride, 10, 112 Methyl -amyI ketone, 10, 60 M ethylation of thiourea, 12, 52 Methyl benzoate, 10, 51 Methyl chloride, 10, 32, 36 Methylene bromide, 10, 112... 

Poisoning has also been used as a means of official execution. The American states that use the gas chamber for executing criminals employ cyanide gas for the purpose. These days a lethal injection is the more usual method of execution. In some states in the USA and in China (which approved this method of execution only in 1997), for example, three chemicals are used. First, a barbiturate drug (sodium thiopental) is injected into a vein (this is called an intravenous injection), which rapidly causes unconsciousness (within thirty seconds). The victim is therefore unaware of what follows. Then pancuronium bromide, a muscle relaxant drug, is injected into the vein, which paralyses the muscles of the diaphragm within about three minutes and so stops respiration. Finally, a... 

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