Adenosine A1 receptors and the anticonvulsant potential of drugs effective in the model of 3-nitropropionic acid-induced seizures in mice.
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.
Zuchora
Beata
B
Department of Pharmacology and Toxicology, Medical University, Jaczewskiego 8, 20-090 Lublin, Poland.
Wielosz
Marian
M
Urbańska
Ewa M
EM
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D003292:Convulsants / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D051379:Mice; D009574:Nitro Compounds; D011422:Propionates / Q000633:toxicity*; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000927:Anticonvulsants; D003292:Convulsants; D009574:Nitro Compounds; D011422:Propionates; D043682:Receptor, Adenosine A1; C015392:3-nitropropionic acid