Molecular Basis of Inhibitory Neurotransmitters

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Chapter: Medicinal Chemistry : Sedatives and Hypnotics

Gamma-aminobutyric acid (GABA) is the main inhibitory transmitter in the brain. GABA is formed from glutamate by the action of glutamic acid decarboxylase.


MOLECULAR BASIS OF INHIBITORY NEUROTRANSMITTERS

Gamma-aminobutyric acid (GABA) is the main inhibitory transmitter in the brain. GABA is formed from glutamate by the action of glutamic acid decarboxylase. Its action is terminated by reuptake, but also by deamination catalyzed by GABA transaminase. There are two types of GABA receptors, that is, GABAA and GABAB. GABAA receptors, which occur mainly postsynaptically, are directly coupled to chloride channels, opening of which reduces membrane excitability. Other drugs that interact with GABA receptors and channels include benzodiazepines, neurosteroids, including endogenous progesterone metabolites and other CNS depressants, such as barbiturates, which facilitate the action of GABA. GABAB receptors are G proteincoupled receptors linked to the inhibition of cAMP formation. They cause pre and postsynaptic inhibition by inhibiting Ca2+ channel openings and increasing K+ conductance. Baclofen is a GABA1 receptor agonist used to treat spasticity. Glycine is another inhibitory transmitter functionally similar to GABA action.


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