Diazepam Diphenylhydantoin

Diphenylhydantoin (23), diazepam (24), phenacemide (25), and ethylphenacemide (26) are all potent anticonvulsants 41 . The first two drugs, though chemically unrelated, have similarities in their three-dimensional structures 42). The other two open-chain acetylurea derivatives 25 and 26 in the crystalline state bear striking stereochemical... 

The action of 44 appears to be similar to that of the anticonvulsant diphenyl-hydantoin (45). Attempts have been made66) to correlate the stereochemical and biological features of 44 with those of chemically different anticonvulsants such as diphenylhydantoin, diazepam, procyclidine, trihexyphenidyl, and ethylphen-acemide. 

In cell culture preparations, diphenylhydantoin, carbamazepine and valproate have been shown to reduce membrane excitability at therapeutically relevant concentrations. This membrane-stabilizing effect is probably due to a block in the sodium channels. High concentrations of diazepam also have similar effects, and the membrane-stabilizing action correlates with the action of these anticonvulsants in inhibiting maximal electroshock seizures. Intracellular studies have shown that, in synaptosomes, most anticonvulsants inhibit calcium-dependent calmodulin protein kinase, an effect which would contribute to a reduction in neurotransmitter release. This action of anticonvulsants would appear to correlate with the potency of the drugs in inhibiting electroshock seizures. The result of all these disparate actions of anticonvulsants would be to diminish synaptic efficacy and thereby reduce seizure spread from an epileptic focus. 

Lorazepam is less lipophilic than diazepam and there is evidence that it has a longer duration of anticonvulsant action than diazepam after intravenous administration. This could be due to the fact that diazepam is more rapidly removed from the brain compartment than lorazepam, which limits its duration of antiepileptic activity. In practice, when diazepam is used to control status epilepticus it is often necessary to continue treatment with diphenylhydantoin, which has a longer duration of action in the brain. The principal hazards of benzodiazepines when given intravenously include respiratory depression and hypotension. Diazepam may be administered rectally, its ease of absorption leading to peak plasma levels within about 10 minutes. 

Figure 6 shows the inhibitory curves obtained with four drugs, each representing a major inhibitory type. Thus diphenylhydantoin binds very strongly to HSA but has no appreciable inhibitory effect. Diazepam... 

GC-MS methods provide greater specificity and in many cases sensitivity when compared with more conventional techniques. They offer increased scope for the study of pharmacokinetics and of plasma concentration in relation to biological effect. SIM assay has been applied to the investigation of placental transfer of lipid soluble drugs and their subsequent elimination in the newborn (barbiturates, diphenylhydantoin, caffeine, pethidine and diazepam [122,408] diphenylhydantoin [411] amylobarbitone and 3 -hydroxyamylobarbitone [83,423]). 

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