Convulsant potencies of tetrazoles are highly correlated with actions on GABA/benzodiazepine/picrotoxin receptor complexes in brain

Richard F. Squires, Else Saederup, Jacqueline Crawley, Phil Skolnick, Steven M. Paul

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

A series of tetrazole convulsants were examined for their potencies in displacing [35S]-t-butylbicyclophosphorothionate (TBPS) from the picrotoxin site on the benzodiazepine-GABA-chloride ionophore receptor complex. All of the tetrazole derivatives tested inhibited [35S]-TBPS binding from rat forebrain membranes, and except for one (undecamethylenetetrazole), had Hill coefficients near unity. Similar to other chemically unrelated convulsants the inhibition of [35S]-TBPS binding by the various tetrazole derivatives was unaffected by the addition of the bicucculine-like GABA antagonist, R 5135. To ascertain whether the inhibition of specific [35S]-TBPS binding by the tetrazole derivatives was related to their convulsant properties, we compared their in vitro potencies in displacing [35S]-TBPS binding with their minimum convulsant potencies in mice. A very good correlation was observed (r=0.96, p<0.001) between their relative affinities for the [35S]-TBPS binding site and their convulsant potencies, indicating that pentamethylenetetrazol and related tetrazoles may produced their convulsant and anxiogenic actions via the GABA-benzodiazepine-chloride ionophore receptor complex.

Original languageEnglish (US)
Pages (from-to)1439-1444
Number of pages6
JournalLife Sciences
Volume35
Issue number14
DOIs
StatePublished - Oct 1 1984
Externally publishedYes

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Tetrazoles
Convulsants
GABA-A Receptors
Benzodiazepines
gamma-Aminobutyric Acid
Brain
Derivatives
RU 5135
GABA Antagonists
Picrotoxin
Prosencephalon
tert-butylbicyclophosphorothionate
picrotoxinin receptor
Rats
Binding Sites
Membranes
1H-tetrazole

ASJC Scopus subject areas

  • Pharmacology

Cite this

Convulsant potencies of tetrazoles are highly correlated with actions on GABA/benzodiazepine/picrotoxin receptor complexes in brain. / Squires, Richard F.; Saederup, Else; Crawley, Jacqueline; Skolnick, Phil; Paul, Steven M.

In: Life Sciences, Vol. 35, No. 14, 01.10.1984, p. 1439-1444.

Research output: Contribution to journalArticle

Squires, Richard F. ; Saederup, Else ; Crawley, Jacqueline ; Skolnick, Phil ; Paul, Steven M. / Convulsant potencies of tetrazoles are highly correlated with actions on GABA/benzodiazepine/picrotoxin receptor complexes in brain. In: Life Sciences. 1984 ; Vol. 35, No. 14. pp. 1439-1444.
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