GABAA receptor protein in the vertebrate central nervous system. GABA is a major inhibitory neurotransmitter in the central nervous system. Upon binding, it triggers the GABAA receptor to open its chloride channel to allow chlorine ions into the neuron, making the cell hyperpolarized sar of barbiturates pdf less likely to fire. GABAA PAMs increase the effect of GABA by making the channel open more frequently or for longer periods.
However, they have no effect if GABA or another agonist is not present. This is called allosteric modulation. In psychopharmacology, GABAA receptor PAMs used as drugs have mainly sedative and anxiolytic effects. The GABAA receptors have historically been a target of drug treatment research.
The earliest compounds were ions, such as bromide. In 1903, the first psychoactive derivative of barbituric acid was synthesized and marketed for headaches.
Within 30 years, many other barbiturates were developed and found use as sedatives, sleep aids and general anesthetics. Although barbiturates fell out of favor, they continue to serve as a short-acting anesthetic and anti-epileptic drugs.
Benzodiazepines were discovered in 1950 and largely replaced the barbiturates because of their larger therapeutic index. At first benzodiazepines were considered to be safe and efficient minor tranquilizers but then were criticized for their dependence producing effects. Several efficient benzodiazepines offer choices about dosage form, length of action, metabolic interaction and safety.