The Effect of 2-Amino-3-Arsonopropionate and 2-Amino-4-Arsonobutyrate on the Development and Maintenance of Amygdala Kindled Seizures

Abstract

The effects of 2-a-3-arsonopropionate and 2-a-4-arsonobutyrate, the arsono analogues of aspartate and glutamate respectively, on the development of electrically-induced kindling in the amygdala, and on seizures induced in fully kindled rats, were compared to the effects of 3-amino-propylarsonate the arsono analogue of GABA.

Intra-amygdaloid micro-injection of 2-a-3-arsonopropionate and 2-a-4-arsonobutyrate (10 nmol in 0.5 μl buffer phosphate) reduced the rate of epileptogenesis without preventing the development of generalized seizure responses, after 14 daily stimulations.

In fully electrically kindled animals with stage 5 amygdala-kindled seizures, 3-aminopropylarsonate (10nmol/0.5 μl) increased after-discharge threshold (ADT) by 82% (P≤0.005) without having any effect on mean seizure score or after-discharge duration. Chemical reduction of 3-aminopropylarsonate with glutathione diminished the anti-seizure activity of the drug. 2-a-3-arsonopropionate and 2-a-4-arsonobutyrate the arsono analogues of aspartate and glutamate were not effective when they were micro-injected into the amygdala of fully kindled animals at equivalent doses i.e. (10nmol/0.5 μl). Higher doses (100nmol/0.5 μl) of 2-a-3-arsonopropionate the analogue of aspartate increased the generalized seizure threshold by 40% (P≤0.025), while 2-a-4-arsonobutyrate was not effective even at high doses.

Keywords:

• Epileptogenesis
• seizures
• amygdala
• 2-amino-3-arsonopropionate
• 2-amino-4-arsonobutyrate
• 3-aminopropylarsonate
• electrical kindling
• GABA analogues
• aspartate
• glutamate