The anti-epileptic effect of 3-aminopropylarsonate on electrically-kindled and N-methyl-D-aspartate-kindled amygdala.

Abstract

The effects of 3-aminopropylarsonate, an arsono analogue of GABA, was tested on the development of electrically-kindled amygdala and on the expression of generalized seizure activity in electrically and NMDA fully amygdala-kindled rats. Intra-amygdaloid microinjection of 3-aminopropylarsonate (10 nmol in 0.5 microl injection vehicle) inhibited electrical epileptogenesis by keeping the seizure score at or below stage 1 on the Racine scale, and the afterdischarge duration (ADD) at or below 19.70 +/- 4.59 s. The effect was reversible after withdrawal of the drug, since the animals developed a generalized seizure activity when kindling stimuli continued in the absence of drug. In fully electrically kindled animals with stage 5 amygdala-kindled seizures, the drug increased afterdischarge threshold (ADT) by 30-70%, without any effect on mean seizure score or ADD. The changes were reversible after 7 days. In fully NMDA-kindled rats, intra-amygdala administration of 3-aminopropylarsonate (10 nmol/0.5 microl) 20 min before injection of NMDA (4 nmol/0.5 microl) reduced the seizure score from 3.80 +/- 0.37(5) on the Racine scale to 0.83 +/- 0.40(6) (P < 0.01). The effect was partially reversible after washing with phosphate buffer. 2-Amino-4-arsonobutyrate, the analogue of glutamate, had no effect on seizure score following treatment with the same concentration of the drug and the same route of injection. The inhibitory effect of 3-aminopropylarsonate on NMDA kindled activity was dose-dependent, since higher doses of NMDA reduced the effect of the drug. The effect of 3-aminopropylarsonate was also selective to NMDA receptors since it had no effect on kainate-induced seizures. With both models of kindling, no gross behavioural abnormalities were observed 3-6 months after treatment with the drug. These findings show the potent antiepileptogenic and anti-convulsant activity of the arsonoanalogue of GABA which appears to be non-toxic and therefore potentially useful as the basis for developing a new family of clinically useful anticonvulsants for treating epilepsy.

• Authors: A S Abdul-Ghani, P J Attwell, H F Bradford
• Journal: Brain research (Brain Res) Vol. 742 Issue 1-2 Pg. 305-12 (Dec 02 1996) ISSN: 0006-8993 [Print] Netherlands
• PMID: 9117409 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arsenicals
• 3-aminopropylarsonic acid
• gamma-Aminobutyric Acid
• N-Methylaspartate

Topics

• Amygdala (drug effects)
• Animals
• Arsenicals (pharmacology)
• Kindling, Neurologic (physiology)
• Male
• N-Methylaspartate (pharmacology)
• Rats
• Rats, Sprague-Dawley
• gamma-Aminobutyric Acid (analogs & derivatives)