Allosteric modulatory centers of transmitter amino acid receptors.
Transmitter amino acid receptors (gamma-aminobutyric acid [GABA] and excitatory amino acids) include in their structure allosteric modulatory centers that regulate the probability of transmitter action. These are sites of action for drugs. In GABA receptors, benzodiazepines and beta-carbolines act as positive and negative modulators. Various subtypes of GABAA receptors exist that differ with regard to the structure of the receptor subunits and the characteristic of the allosteric modulatory centers. This brings up the possibility that classes of benzodiazepines exist that, by acting selectively on specific subtypes of GABAA receptors, may bring about selectivity of drug action in specific anxiety disorders. For instance, clonazepam appears to act better than diazepam on panic attacks and fails to bind to GABAA receptor subtypes located in spinal cord. Also, glutamate receptors and specifically the N-methyl-D-aspartate-sensitive subtype modulated by an allosteric center may include various molecular forms differing with respect to the properties of the allosteric modulatory center. This variability suggests that this center may be used as a target for discovery of drugs acting as specific allosteric modulators of glutamate receptors.
Costa
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Fidia-Georgetown Institute for the Neurosciences, Georgetown University Medical School, Washington, D.C. 20007.
D000494:Allosteric Regulation; D000495:Allosteric Site; D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D008961:Models, Structural; D011963:Receptors, GABA-A / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000502:physiology*
D000596:Amino Acids; D007473:Ion Channels; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter