The anticonvulsant effect of deprenyl on pentylenetetrazol-induced seizures in Lewis rats.
There is recent evidence that deprenyl may have anticonvulsant action in a rat kindling model of epilepsy as well as in a maximal electroshock model. We therefore investigated the effect of deprenyl on the brain sensitivity threshold to pentylenetetrazol (PTZ)-induced maximal seizures in Lewis rats, in a model that provides pharmacodynamic information free of pharmacokinetic interference. The novel finding of this investigation was the anticonvulsant effect of deprenyl following repetitive administration whereas a single deprenyl dose did not affect the PTZ concentrations required to induce maximal seizures. The data suggests that the mechanism of this effect is not associated with the dopaminergic activity of deprenyl since pretreatment with both bromocriptine (a dopamine D2 agonist) and haloperidol (dopamine antagonist) did not affect the seizure threshold, whereas levodopa caused a proconvulsant effect. It was also concluded that the mechanism is not related to changes in acetylcholine levels since prolonged pretreatment with deprenyl did not attenuate the brain sensitivity to pilocarpine-induced seizures. The fact that long term administration of deprenyl was needed to produce its anticonvulsant effect may indicate that the anticonvulsant effect of deprenyl may be due to changes in levels of certain endogenous compounds or down or up-regulation of relevant receptor/effector units.
Hoffman
A
A
Department of Pharmaceutics, School of Pharmacy, Hebrew University of Jerusalem, Israel. ahoffman@cc.huji.ac.il
Afargan
M
M
Backon
J
J
Perlstein
I
I
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use*; D003292:Convulsants / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D008297:Male; D010433:Pentylenetetrazole / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D051381:Rats; D011917:Rats, Inbred Lew; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy*; D012642:Selegiline / Q000494:pharmacology* / Q000627:therapeutic use*
D000927:Anticonvulsants; D003292:Convulsants; D012642:Selegiline; D010433:Pentylenetetrazole