Anticonvulsants GABAa receptors

GABAA receptor antagonist fiYPNOTICS, SEDATIVES, ANTICONVULSANTS, AND ANXIOLYTICS] (Vol 13) Bicyclo[2.2.1]heptan-2-one [497-38-1]... 

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. 

Benzodiazines bind to GABAa receptors, and they have sedative, anxiolytic, muscle relaxant, and anticonvulsant properties. They increase stage 2 sleep and decrease REM and delta sleep. 

The primary action of the benzodiazepines as anticonvulsants is to enhance inhibition through their interaction with the GABAa receptor at the benzodiazepine binding site. However, there appears to be an additional action of benzodiazepines blocking voltage-dependent sodium channels. This effect is not seen at usual doses but is likely a factor in their use in the treatment of status epilepticus (discussed later). 

Zaleplon has a pharmacological profile similar to benzodiazepines. Zaleplon is a full agonist for the benzodiazepine oq receptor located on the GABAa receptor ionophore complex in the brain, with lower affinity for the a2 and a3 subtypes. It selectively enhances the action of GABA similar to but more selectively than benzodiazepines. Zaleplon, although not benzodiazepine-like in chemical structure, induces sedative-hypnotic, anticonvulsant, and anticonflict effects via its binding to the central nervous system (CNS)-type benzodiazepine receptors [33-36]. 

Clonazepam, U5P. Clonazepam S-(2-chlorophenyl)-3-dihydro-7-nitro-2//-1,4-benzodiazpin-2-one (iCIonopin). partially selective at benzodiazepine allosteric binding sites on GABAa receptors, is useful in ab.sence seizures and in myoclonic seizures. Tolerance to the anticonvulsant effect often develops, a common problem with the benzodiazepines. Metabolism involves hydroxylation of the 3 position, followed by glucuronidation and nitro group reduction, followed by acetylation. 

---