Phenobarbital, structure

In this study, potential oscillation was measured in the presence of lOOmM sodium salts of barbital, allobarbital, phenobarbital, and amobarbital in phase wl [19]. Their chemical structures are shown in Fig. 15. Amplitude and the oscillatory and induction periods were noted to depend on the particular hypnotic used. Amplitude decreased in the order, barbital > allobarbital > phenobarbital > amobarbital. The oscillatory period increased in the order, barbital < allobarbital < phenobarbital < amobarbital. Induction period increased in the order, barbital < allobarbital < phenobarbital < amobarbital. These parameters changed depending on drug concentration. Hypnotics at less than 5 mM had virtually no effect on the oscillation mode. 

FIG. 15 Chemical structures of (a) sodium barbital, (b) sodium allobarbital, (c) sodium phenobarbital, and (d) sodium amobarbital. 

Convulsive disorders are still a serious therapeutic problem and new agents are being actively sought. Classical therapy was based upon the barbiturates that are no longer in favor because of their many side effects and their suicide potential. Interestingly, a seemingly minor structural variation of phenobarbital (152, shown as its sodium salt) leads to an anticonvulsant of increased potency and which has less hypnotic activity. In this case, sodium phenobarbital serves as its own base (so the yield is limited to 50%) and reacts readily with... 

Primidone is chemically and structurally similar to phenobarbital with the exception that the carbonyl group on Cj is replaced by a methylene group. This modification leads to the production of a drug with strong anticonvulsant properties without expressed soporific effects. 

A number of drug molecules contain a modified pyrimidine skeleton, the best known examples being the anticancer drug 5-fluorouracil, which is structurally similar to thymine, the antiviral drug AZT, currently being used in the treatment of AIDS, and phenobarbital, a well known sedative. 

PCBs with a more globular structure elicit effects similar to phenobarbital. These include induction of the isozyme CYP2B, carcinogenic promoter activity8 7 and neurotoxicity. Developmental neurotoxicity of PCBs in animals is consistent with findings in children and results in persistent behavioural and neurological effects, notably alterations in motor development and cognitive function.88 The... 

Figure 13.2. Rat and human UGT2A and 2B proteins have a structure similar to that of UGT1A, consisting of divergent and common (or conserved) regions. Some of UGT genes are inducible by phenobarbital or rifampicin through activation of SXR or CAR, heterodimer formation with RXR and bind to regulatory elements in the UGT genes.

Changes in the erythrocytes osmotic resistance were not observed. Adsorption of total plasma proteins on modified MC was lower than 12 %, but it was about 60 - 70 % on unmodified particles. Table 6 summarizes the results obtained of MC sorption efficiency to substances of different molecular mass in donor plasma. The sorption mechanism of low and middle molecular weight substances (phenobarbital and cyanocobalamin) on iron-carbon and restored-iron MC is apparently connected with absorption of molecules into the sorbent s pores. Iron-carbon composites have a more porous structure than restored-iron, therefore the... 

Figure 6 Space-filled molecular structures of cytochromes P450 I substrates and inducers (dibenzanthracene, 9-hydroxyellipticine, and 7-ethoxyresorufin) compared with chemicals that act as substrates for cytochromes P450 II (phenobarbital, metyrapone, and hexobarbital).

Chloroethanes have been shown to undergo dechlorination by an enzyme system that is similar to the hepatic microsomal mixed function oxidase system (Van Dyke and Wineman 1971). Dechlorination was inducible by phenobarbital and required oxygen and NADPH. However, dechlorination also required a factor from the cytosolic fraction of the liver homogenate for optimal dechlorinating activity. In terms of structural requirements, dechlorination was enhanced if the carbon atom containing the chlorine had only one hydrogen. In a microsomal incubation, 13.5% of... 

Bromide (1857) was the first drug to be used for the treatment of epilepsy, but it is now obsolete. Phenobarbital, introduced in 1912, controlled patients resistant to bromides. The next success was the discovery in 1938 of phenytoin (a hydantoin) which is structurally related to the barbiturates. Since then many other drugs have been discovered, but phenytoin still remains a drug of choice in the treatment of major epilepsy. Over the past ten years there has been a dramatic increase in the number of new anticonvulsant drugs (vigabatrin, gabapentin, lamotrigine, topiramate, oxcarbazepine, levetiracetam), but none has been shown to be superior to the major standard anticonvulsants (phenytoin, carbamazepine and sodium valproate). 

These two molecules illustrate how subtle changes in molecular structure can affect action. Amobarbital requires 30 min to take effect and sedation lasts for 5-6 h, while pentobarbital takes effect in 15 min and sedation lasts only 2-3 h. Phenobarbital (R=ethyl, R =phenyl), on the other hand, requires over an hour to take effect, but sedation lasts for 6-10 h. When the alkyl chains are made much longer the sedative properties decrease and the substances become anticonvulsants, which are used to treat epileptic seizures. If the alkyl group is too long or is substituted at one of the two nitrogens, convulsants are produced. 

Nakao, S. Fujii, S. Sakai, T. Tomita, K.-I. The crystal and molecular structure of the 2 1 molecular complex of theophylline with phenobarbital. Acta Crystallogr. 1977, B33, 1373-1378. 

Specificity The specificity of the antiserum was determined by measuring the cross reactivity with substances of a structure similar to that of phenobarbital. The cross reactivity is stated as the ratio of the phenobarbital concentration to the concentration of the cross-reacting substance at a 50% inhibition of the maximal binding. 

By chemical structure—For example, the barbiturates (such as phenobarbital, Amytal, and Seconal) are synthetic compounds derived from the chemical structure... 

Notice the diversity in structure of lhe.se proton dunurs. They include the classical hydrochloric acid (reaction a). Ihc weakly acidic dihydrogen phosphate anion (reaction b). the ammonium cation as is found in ammonium chloride (reaction c), the carboxylic acetic acid (reaction d). Ihc cnolic form of phenobarbital (reaction e), Ihe carboxylic acid moiety of indomelhacin (reaction j), Ihc imidc of saccharin (reaction g). and the prolonaied amine of ephedrine (reaction h). Because all are proton donors, they mu.st be treated as acids when calculating the pH uf a solution or percent ionization of the drug. At the same lime, as nuted below, there are important differences in the pharmaceutical properties of ephedrine hydrochloride (an acid salt of an amine) and lho.se of indomelhacin. phenobarbital. or saccharin. 

---