THE COMPARATIVE PHYSIOLOGICAL ACTIONS OF dl--PHENYLISOPROPYLAMINES I. PRESSOR EFFECT AND TOXICITY

¹ From the Laboratories of George Piness, M.D., Los Angeles and the Pharmacological Laboratory of the University of California Medical School, San Francisco

1. -phenylisopropylamine has a pressor effect on intravenous injection into dogs under barbital anesthesia that is initially equivalent to that of -phenylethylamine and both are about 1/100 to 1/200 as effective as epinephrine. The effect of -phenylisopropylamine is of much longer duration than that of -phenylethylamine and both have effects that are of longer duration than that of epinephrine.

2. -4-hydroxyphenylisopropylamine has a pressor effect on intravenous injection into dogs under barbital anesthesia that is initially equivalent to that of -4-hydroxyphenylethy1amine and both are about 1/50 to 1/100 as effective as epinephrine. The effect of -4-hydroxyphenylisopropylamine is of longer duration than that of -4-hydroxyphenylethylamine and both have effects that are of longer duration than that of epinephrine.

3. -3,4-dihydroxyphenylisopropylamine has a pressor effect on intravenous injection into dogs under barbital anesthesia that is initially equivalent to that of -3, 4-dihydroxyphenylethylamine and both are about 1/50 as effective as epinephrine. The effect of -3, 4-dihydroxyphenylisopropylamine is usually more prolonged than that of -3,4-dihydroxyphenylethylamine and both have effects that are of longer duration than that of epinephrine.

4. The isopropylamine series of compounds is considerably more toxic than the ethylamine series of compounds on subcutaneous injection into guinea pigs. The introduction of one or two hydroxyl groups into the phenyl part of the structure of these compounds results in a lower toxicity in both the isopropylamine and ethylamine series of compounds.

5. Relationships between chemical constitution and physiological action in the series of compounds studied are briefly discussed.