Neuroexcitatory Drug Receptors in Mammals and Invertebrates
Abstract
Previous work by the principal investigators and others has shown that the major type of synaptic receptor for the major inhibitory neurotransmitter, the GABA-A receptor/chloride channel complex, is the target of numerous drugs and toxins. The GABA-A receptor function is directly potentiated by several categories of central nervous system depressants including benzodiazepines, barbiturates, steroid anesthetics, avermectin pesticides, and possibly ethanol. GABA-A receptor function is directly blocked by the GABA antagonist bicuculline, benzodiazepine inverse agonists, convulsant barbiturates, and a series of cyclic convulsant molecules like picrotoxin. These neuroexcitatory GABA blockers include pentylenetetrazol, chlorinated hydrocarbon insecticides like dieldrin and lindane, and the synthetic cage convulsants of Casida, such as t-butyl bicyclophosphorothionate (TBPS), one of the most toxic substances to mammals ever encountered. We demonstrated that these convulsant drugs acted potently on GABA-A receptors in mammals and invertebrates, using a combination of electrophysiology and biochemistry. Structural and pharmacological comparisons of the different subtypes of GABA-A receptors in various species and in various regions of human brain are underway. This will help to define to define the specificity of the neurotransmitter and drug binding sites in the various receptors and should lead to the development of new useful drugs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 16, 1990
- Accession Number
- ADA220255
Entities
People
- Richard W. Olsen
- Thomas A. Miller
Organizations
- University of California, Los Angeles