Beeinflussung der cardiazolkrampfschwelle durch veränderten 5-hydroxytryptamingehalt des zentralnervensystems

Summary

1. The seizure threshold of mice was determined by means of timed i.v. infusion of Pentamethylenetetrazol (Metrazol, Cardiazol), after changing the Serotonin content of the brain by pretreatment with Reserpine, which is known to liberate Serotonin, an inhibitor of amineoxydase activity Iproniazid (IPN), and the precursor of Serotonin 5-Hydroxytryptophan (5-HTP).

2. The facilitation of the tonic extensor seizure response by 5 mg/kg Reserpine was prevented by the previous injection of 100 mg/kg IPN; moreover, after this pretreatment a higher average dose of Metrazol was required to produce extensor seizures, as in controls.

3. IPN 100 mg/kg produced no change of the seizure threshold. A small elevation of the threshold for tonic convulsions was observed after treatment with 50 mg/kg 5-HTP. When the animals were pretreated with IPN, the injection of 5-HTP exerted a distinct elevation of the threshold for tonic convulsions. The same threshold elevation followed the injection of 50 mg/kg Dihydroxyphenylalanin (DOPA) after pretreatment with IPN, while DOPA alone was ineffective.

4. When amine-oxydase activity is inhibited by IPN, an increase of spontaneous activity is exerted by 5-HTP, DOPA and Reserpine. This action, produced by excess of liberated amines, is considered to be related with the observed elevation of threshold for tonic seizures.