Abstract |
The role of adenosine A1 receptors in the activity of drugs and substances protecting against seizures evoked by mitochondrial toxin, 3-nitropropionic acid (3-NPA) was studied in mice. Non-selective A1/A2 adenosine receptor antagonist, aminophylline and selective A1 adenosine receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine ( DPCPX) diminished the anticonvulsive effects of diazepam, phenobarbital, valproate and gabapentin. In contrast, A1/A2 adenosine receptor antagonist, 8-(p-sulfophenyl)theophylline (8pSPT) not penetrating via blood-brain barrier was ineffective. Aminophylline and DPCPX but not 8pSPT also reversed the protective action of A1/A2 adenosine receptor agonist, 2-chloroadenosine (2-CADO) and selective A1 adenosine receptor agonist, R-N6-phenylisopropyloadenosine ( R-PIA), against 3-NPA-evoked convulsions. Obtained results suggest that the central adenosine A1 receptor stimulation may play a role in the anticonvulsive potential of diazepam, phenobarbital, valproate and gabapentin in a novel model of 3-NPA-evoked seizures. Moreover, concomitant application of aminophylline with these drugs may reduce their clinical antiepileptic efficacy, especially among patients suffering from seizures related to the disturbances of mitochondrial respiratory chain.
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Authors | Beata Zuchora, Marian Wielosz, Ewa M Urbańska |
Journal | European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
(Eur Neuropsychopharmacol)
Vol. 15
Issue 1
Pg. 85-93
(Jan 2005)
ISSN: 0924-977X [Print] Netherlands |
PMID | 15572277
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adenosine A1 Receptor Agonists
- Adenosine A1 Receptor Antagonists
- Anticonvulsants
- Convulsants
- Nitro Compounds
- Propionates
- Receptor, Adenosine A1
- 3-nitropropionic acid
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Topics |
- Adenosine A1 Receptor Agonists
- Adenosine A1 Receptor Antagonists
- Analysis of Variance
- Animals
- Anticonvulsants
(therapeutic use)
- Convulsants
(toxicity)
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Drug Interactions
- Male
- Mice
- Nitro Compounds
- Propionates
(toxicity)
- Receptor, Adenosine A1
(physiology)
- Seizures
(chemically induced, drug therapy)
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