GABAergic activity, effects

GABA is the major inhibitory neurotransmitter in the CNS. Similar to the modulation of glutamatergic receptors, the application of ligands that can strengthen or weaken GABAergic activity has widespread effects. 

Potassium bromide appears to stabilize neuronal cell membranes by interfering with chloride ion transport across them. It potentiates the effect of GABA by hyperpolarizing the membrane. Other drugs with GABAergic activity, such as the barbiturates, may act synergistically with potassium bromide to raise the seizure threshold. 

Alcoholism is a major social, economic, and pnblic health problem. Social need and abuse of alcohol induced the development of tolerance and dependence. A literature survey on ethanol and alcoholism indicates that GABA is an important target of ethanol in the CNS. Drinking ethanol alters the activity of GABA. Thus, it is speculated that the initial excitatory effect of ethanol may be due to the inhibition of GABAergic activity and decrease of GABA secretion in the brain. ... 

Benzodiazepines. Several BZs have anticonvulsant activity and ate used for the treatment of epilepsy producing their anticonvulsant actions via interactions with the GABA /BZ receptor complex to enhance inhibitory GABAergic transmission (1). The anticonvulsant actions of the BZs tend to tolerate upon chronic usage in six months, and BZs also lead to withdrawal symptomatology. Other side effects include sedation, ataxia, and cognitive impairment. 

Several groups of CNS active drugs exert all or some of their clinical effects by their action on the GABAergic system. 

It has been suggested that modafinil increases wakefulness by activating ai noradrenergic receptors or hypothalamic cells that contain the peptide hypocre-tin [3], or that it may act by modulating the GABAergic tone that might lead to an increased dopamine release in the nucleus accumbens. On the other hand, modafinil does not have any effect in DAT knockout mice. 

GHB has sedative, anxiolytic, and euphoric effects similar to ethanol, likely because of potentiation of cerebral GABAergic and dopaminergic activities. 

---