Accession Number:

ADA220255

Title:

Neuroexcitatory Drug Receptors in Mammals and Invertebrates

Descriptive Note:

Final rept. 19 Jan 1987-18 Jan 1990

Corporate Author:

CALIFORNIA UNIV LOS ANGELES

Personal Author(s):

Report Date:

1990-03-16

Pagination or Media Count:

9.0

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 receptorchloride 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.

Subject Categories:

  • Toxicology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE