ADRENERGIC BLOCKING EFFECTS OF 4 BENZODIOXANES

The structural formulae of the 4 benzodioxanes are: The intraperitoneal LD₅₀'s of BD-3, 933F, BD-1, and BD-5 in mice were 0.16,0.20, 0.26, and 0.22 g/kg respectively. Deaths of the animals occurred mostly in 1—3 hours for the BD-3 and 933F groups, while those for the BD-1 and BD-5 groups occurred mostly in 1—3 days. BD-5 markedly decreased the toxicity of intraperitoneal epinephrine in mice, whereas the other 3 compounds did not. Intravenous injections of these 4 drugs in anaesthetized rats and cats all produced a fall of blood pressure, but the differences among the hypotensive potencies were nonsignificant. BD-3, 933F, and BD-1 resulted in a reversal of the epinephrine hypertension in anaesthetized cats, while BD-5 yielded merely an inhibition. All these 4 compounds inhibited the pressor effects of tyramine and norepinephrine. Intravenous administration of 10 mg/kg of 933F in anaesthetized cats raised the blood glucose level, but BD-5 did so only at the dosage of 20mg/kg. BD-5 and 933F did not significantly inhibit the epinephrine-induced hyperglycemia and hyperlactacidemia. Since BD-5 blocked both vasoconstrictor and dilator responses and did not cause epinephrine reversal, it might be better than 933F in treating vasospastic diseases. Clinical trial is recommended.