The protective effect of 2-chloroadenosine against the development of amygdala kindling and on amygdala-kindled seizures.
Journal - European journal of pharmacology (NETHERLANDS )
The influence of 2-chloroadenosine, a non-metabolizable adenosine A1 receptor agonist, was tested on the development of electrically kindled amygdala and on the seizure responses of fully kindled rats. Focal intra-amygdaloid injection of 2-chloroadenosine (1-10 nmol/0.5 microl) 20 min before applying the daily kindling stimulus prevented the development of the kindling process. The behavioural seizure score and the afterdischarge duration were reduced below their initial values. The antiepileptogenic effects of 1 and 10 nmol of 2-chloroadenosine were reversible 8-10 days after withdrawal of the drug. When 2-chloroadenosine was tested on fully developed stage 5 amygdala-kindled seizures, it increased the generalised seizure threshold in a dose-dependent manner. A maximum efficiency of 125% (P < 0.001) was achieved with 5 nmol and the median effective dose was 0.55 nmol. Higher doses resulted in the reduced anticonvulsant effect (P < 0.05). With the same daily stimulation, 2-chloroadenosine 5 nmol in 0.5 microl vehicle, significantly reduced the maximum seizure score by 90%, the afterdischarge duration by 88% and completely blocked the generalised seizure duration. The antiseizure activity of the drug lasted for 3 days. In conclusion, 2-chloroadenosine not only acts as an anticonvulsant against electrically induced kindled seizures as described here, and against audiogenic seizures, electroshock and a variety of chemical convulsants as described by others, it prevents the development of the epileptic state by kindling-stimulation, i.e., it is antiepileptogenic. We theorise here that this is due to its blockade of presynaptic glutamate release.
|ISSN : ||0014-2999|
|Mesh Heading : ||2-Chloroadenosine Amygdala Animals Anticonvulsants Behavior, Animal Body Temperature Dose-Response Relationship, Drug Electric Stimulation Injections Kindling, Neurologic Male Rats Rats, Sprague-Dawley Receptors, Presynaptic Seizures administration & dosage drug effects pathology drug effects drug effects drug effects drug effects pathology physiopathology|
|Mesh Heading Relevant : ||pharmacology physiology pharmacology physiology|