Sedative and Hypnotics, and Antiepilepsy agents
What is the chemical name of GABA?
The amino acid derivative, γ-aminobutyrate, also called 4-aminobutyrate, (GABA) is a well-known inhibitor of presynaptic transmission in the CNS. 2.
Explain: the structure of GABAA receptor complex and location of Benzodiazepine’s and barbiturate’s binding sites on GABAA receptors. a.
The GABAA receptor complex have chloride channels associated with in the receptor (influx of Cl cause hyperpolarization causing CNS depression) b.
In this isoform, the two binding sites for GABA are located between adjacent α1 and β2 subunits, and the binding pocket for benzodiazepines (the BZ site of the GABAA receptor) is between an α1 and the γ2 subunit. i.
α1 subunits in GABAA receptors mediate sedation, amnesia, and ataxic effects of benzodiazepine 3.
Describe the difference in the action of barbiturates at lower and higher dose on GABAA receptors a.
BZ increase synaptic inhibition of GABA
They enhance GABAergic effects without directly activating GABAA receptor by opening of chloride channels but by increasing frequency of chloride opening events and enhancing chloride ion conductance. c.
Barbiturates increase the duration of the GABA-gated chloride channel openings d.
At high concentrations, the barbiturates may also be GABA-mimetic, directly activating chloride channels. e.
Barbiturates are less selective in their actions than benzodiazepines, because they also depress the actions of the excitatory neurotransmitter glutamic acid via binding to the AMPA receptor (can cause full surgical anesthesia and pronounced central depressant effects – low margin of safety). f.
If GABA is not present, benzodiazepines cannot produce their effects (they can increase the frequency but cannot initiate; only GABA opens the channels). 4.
Name GABAA and GABAB receptor agonist
GABAA is the major inhibitory neurotransmitter in spinal cord, hypothalamus, hippocampus,...
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