Barbiturate anticonvulsants

Urea and malonic acid give barbituric acid (7), a key compound in medicinal chemistry (see also Hypnotics, SEDATIVES, AND anticonvulsants) ... 

Phenytoin. Phenytoin sodium is sodium diphenylhydantoin [630-93-3] which is stmcturally related to the barbiturates. It was originally introduced as an anticonvulsant (18) (see Hypnotics, sedatives, and anticonvulsants) and later found to have antiarrhythmic properties (19), although not approved by the PDA for any arrhythmic indications. Phenytoin is effective in the treatment of ventricular arrhythmias associated with acute MI and with digitalis toxicity (20). It is not very effective in treatment of supraventricular arrhythmias (20). 

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>. 

P-Blockers, benzodiazepines, NSAIDs, barbiturates NSAIDs, protease inhibitors, P-blockers, benzodiazepines Antimalarials, NSAIDs, P-blockers, bronchodilators Phosphine oxides, NSAIDs, anticonvulsants Bronchodilators, P-blockers... 

Paraldehyde, a miscellaneous sedative and hypnotic, may be used to treat delirium tremens and other psychiatric conditions. In addition, some barbiturates are used as anticonvulsants (see Chap. 28). 

The effects of the progestins are decreased when administered with anticonvulsants, barbiturates, or rifampin. Administration of the penicillins or tetracyclines with the oral contraceptives decreases the effects of the oral contraceptives. 

Long-acting barbiturates used as sedative-hypnotics and also for their anticonvulsant effects include phenobarbital (Luminal) and mephobarbital (Mebaral). 

The pharmacokinetics of batbitutates have been discussed by Chatney et al. (2001) and Harvey (1985). When used as hypnoticsotantianxiety agents, the barbiturates ate administeted otaUy. As anticonvulsants, they may be used either orally or intravenously, although the lattet toute of administtation may be problematic because these dtugs ate vety alkaline and nectosis and pain oc-cut at the site of injection. 

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). 

PCP, like barbiturates, also has anticonvulsant effects in various animal models (Chen et al. 1959 Geller et al. 1981 Hayes and Balster 1985). Certain convulsants, such as strychnine, are not antagonized, and PCP has some specificity for tonic rather than clonic convulsions. 

Benzodiazepines are the evidence-based treatment of choice for uncomplicated alcohol withdrawal.17 Barbiturates are not recommended because of their low therapeutic index due to respiratory depression. Some of the anticonvulsants have also been used to treat uncomplicated withdrawal (particularly car-bamazepine and sodium valproate). Although anticonvulsants provide an alternative to benzodiazepines, they are not as well studied and are less commonly used. The most commonly employed benzodiazepines are chlordiazepoxide, diazepam, lorazepam, and oxazepam. They differ in three major ways (1) their pharmacokinetic properties, (2) the available routes for their administration, and (3) the rapidity of their onset of action due to the rate of gastrointestinal absorption and rate of crossing the blood-brain barrier. 

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... 

Barbiturate The family name for a group of drugs with anticonvulsant, anaesthetic and sedative-hypnotic properties. Examples include amylobarbitone and pheno-barbitone. The problem of dependence and the introduction of safer benzodiazepine alternatives has resulted in a marked reduction in their clinical use. 

Anticonvulsants (barbiturates, including phenobar-bital and primidone carbamazepine felbamate phenytoin topiramate vigabatrin)... 

Zolpidem, chemically unrelated to benzodiazepines or barbiturates, acts selectively at the y-aminobutyric acidA (GABAA)-receptor and has minimal anxiolytic and no muscle relaxant or anticonvulsant effects. It is comparable in effectiveness to benzodiazepine hypnotics, and it has little effect on sleep stages. Its duration is approximately 6 to 8 hours, and it is metabolized to inactive metabolites. Common side effects are drowsiness, amnesia, dizziness, headache, and GI complaints. Rebound effects when discontinued and tolerance with prolonged use are minimal, but theoretical concerns about abuse exist. It appears to have minimal effects on next-day psychomotor performance. The usual dose is 10 mg (5 mg in the elderly or those with liver impairment), which can be increased up to 20 mg nightly. Cases of psychotic reactions and sleep-eating have been reported. 

This compound is a closely related analogue of the anticonvulsant barbiturate phenobarbitone (phenobarbital Part 111, Volume 8), in wliich the 2-carbonyl... 

Alkyl and 1-aralkyl-5,6-dihydrouracils (LXXIX), prepared by condensation of A -(2-carbamoylalkyl)aralkylamines with urea or by treating a suitable primary amine with an ester of acrylic acid followed by cyanic acid, are CNS depressants and anticonvulsants [639, 640], as well as anti-inflammatory agents [641]. Such compounds are to be compared with the corresponding barbituric acid derivatives in which not more than one hydrogen in the 5-position is substituted, and also with barbiturates in which the 5,5-substituents are similar to the R and groups of the 5,6-positions here. 

---