Barbiturates mechanism of action is described here. Barbiturates most likely produce their sedative hypnotic effects through an interaction with the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the CNS.
Barbiturates cause reversible depression of all excitable tissues, the CNS being exquisitely sensitive. They bind to beta subunit of the inhibitory GABA-A receptor, a site distinct from the site at which benzodiazepines bind.
The interaction of barbiturates with specific membrane components of GABAA receptors appears to decrease the rate of dissociation of GABA from these receptors, thereby increasing the duration of the GABAA-activated opening of chloride channels.
The ability of barbiturates to uniquely depress the reticular activating system, which is presumed to be important in the maintenance of wakefulness, may reflect the ability of barbiturates to decrease the rate of dissociation of GABA from its receptors.
Barbiturates mechanism of action can also mimic the action of GABA by directly activating GABAA receptors. In addition to GABA, barbiturates also inhibit the uptake of aspartate and glutamate.
Barbiturates mechanism of action target nicotinic acetyicholine receptors at concentrations that are achieved with clinical use of these drugs. Barbiturates bind to both open and closed states of the AChR and block the flow of ions through the channel. S(-)-thiopentone was found to be approximately 2 fold more potent than R(+)-thiopentone in the potentiation of GABA at GABAA receptors.
At lower doses, they enhancc the action of GABA whereas in thcrapcutic doses they open the chloride channels directly. They also inhibit the exitatory AMPA-glutamate receptors.