Pharmacology of beta-phenylethylamine-induced seizures in mice

The endogenous trace amine beta-phenylethylamine (PE) produced tonic-clonic seizures in male Swiss mice when administered in doses of 125-200 mg/kg. The number of mice exhibiting PE-induced seizures, the latency to onset of first seizure and the latency to loss of the righting reflex were dose dependent. Pretreatment with the benzodiazepines diazepam, chlordiazepoxide, midazolam and clonazepam significantly reduced the incidence of PE-induced seizures. Similarly, increasing brain gamma-aminobutyric acid (GABA) levels by injection of the GABA-transaminase inhibitors aminooxyacetic acid or gabaculine afforded significant protection against PEA's convulsant effects. The data suggest that PE when administered at high doses may interfere either directly or indirectly with GABAergic neurotransmission in the central nervous system. In addition, since PE induces an epileptiform spiking pattern and produces seizures in rodents it appears possible that the amine may play a role in some forms of human epilepsy.