Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Life sciences (1973), 1984-10, Vol.35 (14), p.1439-1444

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

1984

Quelle

Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)

Beschreibungen/Notizen

• 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.