Pharmacology of dextroamphetamine-induced cardiovascular malformations in the chick embryo.
We have observed dextroamphetamine sulfate to cause cardiovascular malformations in the 4-day-old chick embryo. Essentially all malformations were of the heart and great vessels. About one-half of these were the abnormal persistence of the left fourth aortic arch. Ventricular septal defects comprised the vast majority of the other malformations. Since d-amphetamine has both a direct and, more importantly, an indirect mode of alpha and beta adrenergic stimulation, three drugs were used to try to inhibit malformation production: alpha-methyl-p-tyrosine (AMT), a catecholamine synthesis inhibitor; metoprolol, a beta 1 blocker; and phentolamine, an alpha blocker. When given with d-amphetamine, all three drugs significantly reduced the malformation rate resulting from d-amphetamine alone. We speculate that the embryonic chick is capable of responding to the alpha and/or beta properties of dextroamphetamine sulfate. These properties may be causally related to the malformations observed.
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control; D000818:Animals; D002642:Chick Embryo; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000517:prevention & control; D008781:Methyltyrosines / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D008781:Methyltyrosines; D019805:alpha-Methyltyrosine; D008790:Metoprolol; D003913:Dextroamphetamine; D010646:Phentolamine