Intravenous, cortical and intraventricular dose-effect relationship of pentylenetetrazol, picrotoxin and deslanoside in dogs

The dose-route-effect relationship of pentylenetetrazol, picrotoxin, and deslanoside when given intravenously, subarachnoidally on the cortex, and in the lateral ventricle, the third ventricle, and the fourth ventricle, was determined in dogs with cannula or catheter chronically implanted in the various regions of the brain. Pentylenetetrazol and picrotoxin produced EEG convulsive discharges when given intravenously or applied cortically or intraventricularly. The most sensitive target area was the cortex. Pentylenetetrazol exhibited the quickest onset and the shortest duration of action; picrotoxin acted slower and longer. Deslanoside produced convulsive discharges only when applied cortically or intraventricularly, but not intravenously. The most sensitive target area were the subcortical structures. Cardiac arrhythmias were produced with pentylenetetrazol, picrotoxin, and deslanoside. The most sensitive target area was the fourth ventricle. Cardiac arrhythmias also occurred after third and lateral ventricle injection, but only rarely after cortical injection and then with large doses. They occurred with or without EEG convulsive discharges. The blood pressure was increased by pentylenetetrazol, picrotoxin, and deslanoside, usually concomitantly with the EEG convulsive discharges and/or cardiac arrhythmias. Increase in blood pressure started just prior to the occurrence of the first spikes and was accompanied by tachycardia. This hypertension is also of central origin and is manifested after various cerebral routes of administration. EEG convulsive discharges induced by pentylenetetrazol applied by intravenous versus cortical route exhibited a dose-effect relationship of approximately 6 to 1; picrotoxin 1000 to 1; and deslanoside > 300 to 1.