Effects of anesthesia and phenoxybenzamine on responses of dogs to IV subtoxic doses of 3,4-methylenedioxyamphetamine (MDA).

Racemic 3,4-methylenedioxyamphetamine HCl (MDA) was tested for acute intravenous (i.v.) lethality in mongrel dogs. The LD50 and 95% confidence limits were 8.1 (7.0-9.4) mg/kg, and the LD1 and LD99 were approximately 5 and 14 mg/kg. Subtoxic doses (0.1, 0.3, 1.0 and 3.0 mg/kg, i.v.) were tested for acute effects on cardiovascular and respiratory functions in conscious dogs prepared surgically under local anesthesia and also in dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Four experimental groups were constituted, by pretreating or not, both conscious and anesthetized dogs with phenoxybenzamine HCl (15 mg/kg, i.v.). Arterial and left ventricular pressures tended to be elevated more by MDA in the anesthetized than in the conscious dogs. These and other cardiovascular parameters tended to be more fully antagonized by phenoxybenzamine in anesthetized than in conscious dogs. Respiratory rate was increased by higher doses, more so in the conscious group, but the increase was fully blocked by phenoxybenzamine. Possible clinical implications of the data are suggested.