EFFECTS OF A NEW DIBENZAZEPINE DERIVATIVE, RO 2-3248, 6-ALLYL-6,7-DIHYDRO-5H-DIBENZ[c,e]AZEPINE PHOSPHATE, UPON THE BLOOD FLOW, THE PERIPHERAL RESISTANCE AND THE RESPONSE TO INJECTIONS OF EPINEPHRINE OF THE INNERVATED HIND LIMB OF THE DOG

¹ Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest College, Winston-Salem, N. C.

1. The responses to a new dibenzazepine, adrenergic blocking drug, Ro 2-3248, and to epinephrine before and after the Ro 2-3248 were studied by recording their effects on the blood flow in the femoral artery of a normally innervated dog's leg; measurments were made with an electronically operated, differential pressure, direct writing, flowmeter.

2. When injected intra-arterially in doses of 0.3 to 10 mgm., Ro 2-3248 proved to be a prompt, moderately long-lasting vasodilator. Tachyphylaxis was not seen with repeated intra-arterial injections of 0.5 mgm. of Ro 2-3248.

3. One microgm. of epinephrine intra-arterially always induced pure vasoconstriction. After an average dose of 0.97 mgm./kgm. (8.9 mgm.) of Ro 2-3248 intra-arterially, the response to 1 microgm. of epinephrine injected intra-arterially was pure vasodilation. This reversal of response persisted in the different experiments for from 1 hour and 17 minutes to 5 hours and 36 minutes. The normal vasoconstrictor response to epinephrine was blocked for a considerably longer period.

4. One mgm./kgm. of Ro 2-3248 intravenously produced a prolonged fall in arterial blood pressure and reversed the flow response to intravenous injections of 1 microgm./kgm. of epinephrine for approximately three-quarters of an hour.

5. Ro 2-3248 in a dose sufficient to reverse the response to 1 microgm. of epinephrine, reversed the blood flow response to all doses up to 60 microgm. of epinephrine injected intra-arterially.

6. Increasing the dose of Ro 2-3248 to 2 to 4 mgm./kgm. did not cause the vasodilator response to 1 microgm. of epinephrine to be any greater than that seen with the 1 mgm./kgm. dose just necessary to reverse fully the flow response to this dose of epinephrine.

7. Milligram for milligram Ro 2-3248 intra-arterially was as effective as Priscoline, and about one-sixth as effective as Regitine in reversing the response to intra-arterial injections of 1 microgm. of epinephrine, but the reversal lasted longer than that of either of the latter two drugs.

8. Doses of Ro 2-3248 up to 16 mgm./kgin. given as an intravenous infusion to anesthetized dogs over a half hour period caused no fatalities.

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