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 language | English (US) |
|---|---|
| Pages (from-to) | 1439-1444 |
| Number of pages | 6 |
| Journal | Life Sciences |
| Volume | 35 |
| Issue number | 14 |
| DOIs | |
| State | Published - Oct 1 1984 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Convulsant potencies of tetrazoles are highly correlated with actions on GABA/benzodiazepine/picrotoxin receptor complexes in brain
AU - Squires, Richard F.
AU - Saederup, Else
AU - Crawley, Jacqueline
AU - Skolnick, Phil
AU - Paul, Steven M.
PY - 1984/10/1
Y1 - 1984/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0021122793&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021122793&partnerID=8YFLogxK
U2 - 10.1016/0024-3205(84)90159-0
DO - 10.1016/0024-3205(84)90159-0
M3 - Article
C2 - 6090836
AN - SCOPUS:0021122793
VL - 35
SP - 1439
EP - 1444
JO - Life Sciences
JF - Life Sciences
SN - 0024-3205
IS - 14
ER -