Barbiturates antiseizure action

Most barbiturates have antiseizure properties. The discussion below is limited to the two barbiturates that exert maximal antiseizure action at doses below those required for hypnosis, a property that determines their clinical utility as antiseizure agents. The pharmacology of barbiturates is considered in Chapter 16. 

The barbiturates are substituted pyrimidine derivatives with an ureide configuration (Fig. 20.4). They are lipophilic weak acids (pKa 7-8) that are weii distributed into brain (see Appendix A for the respective pKa values). Although many barbiturates dispiay sedative-hypnotic activity (see Chapter 19), oniy a few have antiseizure properties. Paradoxically, many barbiturates cause convulsions at larger doses. The barbiturates clinically useful as AEDs are phenobarbital, mephobarbital, and primidone (Fig. 20.8). In laboratory animals, phenobarbital is effective by several tests in nontoxic doses. It is active against electrically induced seizures (MES), and it elevates the threshold for pentylenetetrazole stimulation. The mechanism of antiseizure action for the barbiturates... 

Mechanism of Action. Barbiturates are known to increase the inhibitory effects of GABA (see Chapter 6), and this effect is probably the primary way that these drugs decrease seizure activity. Barbiturates may also produce some of their antiseizure effects by inhibiting calcium entry into excitatory presynaptic nerve terminals and thereby decreasing the release of excitatory neurotransmitters such as glutamate.20... 

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