Barbiturates anticonvulsant activity

Pharmacology These agents depress the sensory cortex, decrease motor activity, alter cerebellar function, and produce drowsiness, sedation, and hypnosis. Barbiturates have little analgesic action at subanesthetic doses and may increase the reaction to painful stimuli. All barbiturates exhibit anticonvulsant activity in anesthetic doses. However, only phenobarbital and mephobarbital are effective as oral anticonvulsants in subhypnotic doses. 

RPC has found use in the analysis of barbiturates including the determination of drugs taken in an overdose (332). Thiopental was determined using a mobile phase comprised of methanol-0.1% sodium citrate buffer, pH 6.5 (45 55) (333). Hydantoins, along with other species which have anticonvulsant activity, have been determined with barbiturates. These include phenytoin in the presence of phenobarbital and primidone (334,335) and the related anticonvulsants ethosuximide and carbamazepine (336). 

Hamor and Lien have analyzed anticonvulsant activities of sulfamoyl-benzoates. For the test of antistrychnine activity, compounds having the same aromatic substituents are used so that no 2o-(X,Y) term appears in Equation 22. They have suggested that the similarity of equations in terms of steric, hydrophobic, and electronic properties of substituents indicates a common anticonvulsant mechanism for the two biological effects of this set of compounds. They have also suggested that the mechanism of action of these drugs was quite different from those of barbiturates and other hypnotics where quite different structure-activity correlations of physicochemical significance have been obtained. 

Klopman, G. and Raychaudhury, C. (1990). Vertex Indices of Molecular Graphs in Structure-Activity Relationships A Study of the Convulsant-Anticonvulsant Activity of Barbiturates and the Carcinogenicity of Unsubstituted Polycyclic Aromatic Hydrocarbons. J. Chem. Inf ComputSci.,30,12-19. 

Mopman, G. and Raychaudhury C. (1990) Vertex indices of molecular graphs in structure-activity relationships a study of the convulsant— anticonvulsant activity of barbiturates and the carcinogenicity of unsubstituted polycyclic aromatic hydrocarbons. /. Chem. Inf. Comput. Sci., 30, 12-19. 

The barbiturates can produce all degrees of depression of the CNS, ranging from mild sedation to general anesthesia. The use of barbiturates for general anesthesia is discussed in Chapter 13. Certain barbiturates, particularly those containing a 5-phenyl substituent (e.g., phenobarbital and mephobarbitaU have selective anticonvulsant activity (see Chapter 19). The antianxiety properties of the barbiturates are inferior to those exerted by the benzodiazepines. 

Except for the anticonvulsant activities of phenobarbital and its congeners, the barbiturates possess a low degree of selectivity and therapeutic index. Thus, it is not possible to achieve a desired effect without evidence of general depression of the CNS. Pain perception and reaction are relatively unimpaired until the moment of unconsciousness, and in small doses, the barbiturates increase the reaction to painful stimuli. Hence, they cannot be relied on to produce sedation or sleep in the presence of even moderate pain. 

Properties of the compounds illustrated in Figure 8.11. These pharmacokinetic effects occur in addition to the functional effects of modifications in barbiturate structure. In particular, substitutions at positions Rj and R2 produce agents with increased hypnotic potency and anticonvulsant activity. 

Klopman, G Raychaudbury, C. Vertex Indicies of Molecular Graphs in Structure-activity lationships a Study of the Convulsant-anticonvulsant Activity of Barbiturates and the Carcinogens of Unsubstituted Polycyclic Hydrocarbons". J. Chem. Inf. Comput. Sci. 1990, 30, 12-19. 

The pseudo-barbiturate , 2-methyl-3-o-tolylquinazolin-4(3H)-one (methaqualone, Revonal 1017) has an even wider spectrum of activities than do the barbiturates proper it appears to be quite widely used as- a sedative, hypnotic, anticonvulsant, antispasmodic and local anaesthetic agent (63MI21301, b-75MI21301>. 

There are similarities between the biological actions of inhalants and those of alcohol and barbiturates (Bowen et al. 1996b). For example, acute administration of inhalants affects motor coordination (Moser and Balster 1981) and induces anxiolysis, whereas chronic administration is associated with physical dependence and withdrawal (Bowen et al. 1996a Evans and Balster 1991, 1993). In addition, some inhalant drugs have anticonvulsant properties (Wood et al. 1984). Like other CNS-depressant agents, inhalants have biphasic effects on spontaneous locomotor activity in rodents, with increased activity seen at lower doses and diminished locomotion seen at higher doses (Cause et al. 1985 Kjellstrand et al. 1985). 

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... 

---