Displacement of Brain and Heart Noradrenaline byp‐Hydroxynorephedrine after Administration ofp‐Hydroxyamphetamine

After the administration ofp‐hydroxyamphetamine 20 mg/kg intraperitoneally, there was a 50 per cent decrease in the brain noradrenaline (NA) level and a 70 per cent decrease in the heart NA level at 4–8 hours after the injection. Control levels of brain and heart NA were reached at 96–144 hours after a single dose of the drug. Repeated injections ofp‐hydroxyamphetamine, 20 mg/kg twice daily for 3 days, caused a depletion of brain and heart NA to about 20 per cent of the control levels. The brain dopamine (DA) level was reduced to 85 per cent of the control level at 1 hour after 20 mg/kg of the drug and to 76 per cent after 40 mg/kg. After the repeated injections ofp‐OH‐A, the brain DA was reduced to 70 per cent of the control level. Radioactively labelledp‐hydroxynorephedrine was isolated from both brain and heart tissue extracts after the administration ofp‐hydroxyamphetamine‐3H. Parahydroxynorephedrine‐3H remained in the brain and the heart as long as the NA levels were decreased. The NA deficit in the brain and heart corresponded approximately to the amounts ofp‐hydroxynorephedrine‐3H present in the tissues. In reserpine pretreated rats the amounts ofp‐hydroxynorephedrine‐3H formed in the brain and heart tissues were reduced, indicating thatp‐hydroxynorephedrine is bound by a reserpine sensitive storage mechanism. Administration ofp‐hydroxyamphetamine or amphetamine accelerated the disappearance of labelledp‐hydroxynorephedrine from the brain and the heart.