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Molecular Pharmacology

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Abstract

Chronic caffeine or theophylline exposure reduces gamma-aminobutyric acid/benzodiazepine receptor site interactions.

D J Roca, G D Schiller and D H Farb
Molecular Pharmacology May 1988, 33 (5) 481-485;
D J Roca
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G D Schiller
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D H Farb
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Abstract

Methylxanthines, such as caffeine and theophylline, are adenosine receptor antagonists that exert dramatic effects upon the behavior of vertebrate animals by increasing attentiveness, anxiety, and convulsive activity. Benzodiazepines, such as flunitrazepam, generally exert behavioral effects that are opposite to those of methylxanthines. We report the finding that chronic exposure of embryonic brain neurons to caffeine or theophylline reduces the ability of gamma-aminobutyric acid (GABA) to potentiate the binding of [3H]flunitrazepam to the GABA/benzodiazepine receptor. This theophylline-induced "uncoupling" of GABA- and benzodiazepine-binding site allosteric interactions is blocked by chloroadenosine, an adenosine receptor agonist, indicating that the chronic effects of theophylline are mediated by a site that resembles an adenosine receptor. We speculate that adverse central nervous system effects of long-term exposure to methylxanthines such as in caffeine-containing beverages or theophylline-containing medications may be exerted by a cell-mediated modification of the GABAA receptor.

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Molecular Pharmacology
Vol. 33, Issue 5
1 May 1988
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Abstract

Chronic caffeine or theophylline exposure reduces gamma-aminobutyric acid/benzodiazepine receptor site interactions.

D J Roca, G D Schiller and D H Farb
Molecular Pharmacology May 1, 1988, 33 (5) 481-485;

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Abstract

Chronic caffeine or theophylline exposure reduces gamma-aminobutyric acid/benzodiazepine receptor site interactions.

D J Roca, G D Schiller and D H Farb
Molecular Pharmacology May 1, 1988, 33 (5) 481-485;
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