Receptors for GABA

F. Matsumura There are certainly other such examples. One that comes to mind is the carbamate insecticides which came originally from a natural product model. Although I think it is true that every 10 or 20 years someone will discover a completely new structure with a new mode of action such as Merck has done with the avermectins, there may come a time when we run out of really good models for synthesis. Then we may want to come back to some of the older but proven targets such as GABA receptors for the design of new insecticides. 

FIGURE 12-3 lonophore receptors for neurotransmitters are composed of subunits with four transmembrane domains and are assembled as tetramers or pentamers (at right). The predicted motif shown likely describes nicotinic cholinergic receptors for ACh, GABA receptors for gamma-aminobutyric acid, and receptors for glycine. 

Buspirone. Buspirone (3) hydrochloride has been approved for the symptomatic management of generali2ed anxiety disorder (Table 3). This dmg is of special iaterest because it does not exert its therapeutic actions via modulation of the GABA receptor complex. This compound is stmcturaHy... 

Synaptic vesicles mediate the release of small molecules other than classical neurotransmitters and neuropeptides. Of these, zinc and ATP are the best characterized. NMDA and GABA receptors contain binding sites for zinc, and zinc exerts a direct effect on... 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

Dr. John E. Casida from the University of California Berkeley is inveshgating the fundamental basis for the selective toxicity of insecticides, including endosulfan, acting at the gamma-aminobutyric acid (GABA) receptor of mammals and insects. The research is sponsored by the National Institute of Environmental Health Sciences. 

Resistance to DDT has been developed in many insect species. Although there are some cases of metabolic resistance (e.g., strains high in DDT dehydrochlorinase activity), particular interest has been focused on kdr and super kdr mechanisms based upon aberrant forms of the sodium channel—the principal target for DDT. There are many examples of insects developing resistance to dieldrin. The best-known mechanism is the production of mutant forms of the target site (GABA receptor), which are insensitive to the insecticide. 

---