Anticonvulsant activity of carbamazepine and N6-L-phenylisopropyladenosine in rabbits. Relationship to adenosine receptors in central nervous system.
The present work deals with an EEG and behavioral study on the effects of carbamazepine (CBZ) and N6-L-phenylisopropyladenosine (L-PIA) against the convulsions due to caffeine and pentylenetetrazole (PTZ) in rabbits. Pretreatment with L-PIA (1, 3 and 4 mg/kg) caused a dose-related inhibition of the motor convulsions and the EEG "grand mal" ictal seizure induced by caffeine (75 mg/kg IV). On the contrary, L-PIA given at the high dose of 5 mg/kg IV partially inhibited the EEG and motor seizures elicited by PTZ (20 mg/kg IV). CBZ completely antagonized the EEG and motor convulsions induced by caffeine, while exerted only a protective action towards the EEG and motor convulsions due to PTZ. The administration of an ineffective dose of CBZ (5 mg/kg IV) was able to enhance the protective action of L-PIA towards caffeine-induced convulsions. This synergistic action between CBZ and L-PIA is also present towards the spike-and-wave complexes elicited by PTZ (10 mg/kg). These results confirm that the purinergic system plays an important role in the regulation of the CNS excitability. They suggest therefore, that the anticonvulsant properties of CBZ may be at least partially explained by an influence of this drug on the purinergic system.
Popoli
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P
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
Benedetti
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M
Scotti de Carolis
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A
D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002110:Caffeine / Q000633:toxicity; D002220:Carbamazepine / Q000494:pharmacology*; D002490:Central Nervous System / Q000378:metabolism; D004347:Drug Interactions; D004569:Electroencephalography; D008297:Male; D010433:Pentylenetetrazole / Q000633:toxicity; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D011817:Rabbits; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism
D000927:Anticonvulsants; D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D002220:Carbamazepine; D002110:Caffeine; D000241:Adenosine; D010433:Pentylenetetrazole