Barbiturates binding

Like benzodiazepines, barbiturates bind to the GABA receptor— however, at a different site from the benzodiazepines. Measurements of mean ion channel open times show that barbiturates act by increasing the proportion of channels opening to the longest open state (i.e., 9 msec), resulting in an overall increase in CL flux into the neuron. 

Chang SK et al (1991) Hydrogen-bonding and molecular recognition - synthetic, complex-ation, and structural studies on barbiturate binding to an artificial receptor. J Am Chem Soc 113 7640-7645... 

Barbiturates bind to barbiturate receptors on the chloride channel (see Figure, question 5). Activation of the receptor potentiates the effects of GABA, and increases chloride flux across the neuronal membrane, causing partial hyperpolarization of the neuronal membrane, and decreased conduction. Because the barbiturate receptor is adjacent to both the benzodiazepine receptor and GABA receptor on the channel, the action of barbiturates enhances not only the binding of GABA to its receptor, but the receptor binding of benzodiazepines as well. 

A barbiturate, such as phenobarbital, is a depressant. Barbiturates bind to a receptor for GABA. This keeps channels for chloride ion, CP", transmission open. 

Chang, S. K., Van Engen, D., Fan, E.and Hamilton, A. D. (1991) Molecular Recognition and Hydrogen Bonding Synthetic, Complexadon and Structural Studies on Barbiturate Binding to a Synthetic Receptoi J. Am. Chem. Soc. 113, 7640. 

Most of the barbiturates have been largely replaced with benzodiazepines since the 1960s because of their addictive potential. Barbiturates bind with GABA-receptors. The 3-D structure of GABA-receptors has not heen fiilly experimentally defined yet. 

Barbiturates bind with GABA-receptors and this proiongs the time of the chioride channei opening. Consequentiy the nerve poiarisation is decreased. 

GABAa is a protein with a pentameiic group of subunits (Fig. 4.7). Each subunit has approximately 200 amino acids. There are arormd fom hydrophobic regions which enable the receptor to possess allosteric pockets for interactions, and the hydrophobic region is also important to anchor the protein into the cell membrane. Barbiturates bind with a site different from the site of binding of benzodiazepines, which bind at the active site rather than changing the receptor conformation via an allosteric interaction. 

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