Convulsant and anticonvulsant actions in DBA/2 mice of compounds blocking the reuptake of GABA

Abstract

Compounds blocking the uptake of GABA into neurones or glia have been injected intracerebroventricularly (icv) or intraperitoneally (ip) in DBA/2 mice, age 21–28 days. Protection against audiogenic seizures was seen 30 min after the icv injection of (+)-2,4-diaminobutyric acid (0.5–2.0 μmoles), (±)-nipecotic acid (1.6–3.2 μmoles), (+)-ethyl nipecotate (0.4–0.8 μmoles), (−)-piperazic acid (4 μmoles) and putrescine (2 μmoles) or the ip injection of (+)-2,4-diaminobutyric acid (4–8 mmoles/kg and (+)-ethyl nipecotate (0.24–0.32 mmoles/kg). Of these ethyl nipecotate and nipecotic acid were the most effective anticonvulsants icv, but nipecotic acid was ineffective ip. Limb myoclonus and other epileptic manifestations (rearing, wild running, tonic clonic seizures) occurred in the absence of auditory stimulation after (+)-2,4-diaminobutyric acid (0.5–2.0 μmoles), (±)-cis-3-aminocyclohexane carboxylic acid (3.2–6.4 μmoles) and putrescine (2 μmoles). β-Alanine (2–4 μmoles, icv) depressed respiration but did not protect against audiogenic seizures or induce myoclonus.