EFFECT OF TRANS-2-PHENYLCYCLOPROPYLAMINE UPON NOREPINEPHRINE CONCENTRATION AND MONOAMINE OXIDASE ACTIVITY OF RAT BRAIN

¹ Research and Development Division, Smith Kline & French Laboratories, Philadelphia, Pennsylvania

A maximum increase of 85 to 90% in norepinephrine concentration of rat brain was attained about 5 hours after the oral administration of 5 mg/kg of trans-2-phenylcyclopropylamine (SKF 385) and 8 hours after the oral administration of 100 mg/kg of iproniazid. The levels returned to normal after about 7 days.

Following an oral dose of 5 mg/kg of SKF 385, the monoamine oxidase activity of rat brain was completely inhibited within 60 minutes. The inhibition remained complete until the end of the 16th hour, after which time the activity was slowly restored to normal levels in about 5 days. With 100 mg/kg of iproniazid, inhibition was complete within 3 hours and lasted until the end of the 16th hour. Normal activity was restored after 11 days.

Assuming that brain norepinephrine is metabolized chiefly via monoamine oxidase, it was estimated from the rate of increase of the amine concentration, following in vivo inhibition of the enzyme by SKF 385, that the turnover rate of norepinephrine in the brain is 17%/hour.

The possibility of the participation of the O-methyl transferase system in the metabolism of norepinephrine in rat brain is discussed.