THE ROLE OF ENDOGENOCS NOREPINEPHRINE IN THE TOXICITY OF d-AMPHETAMINE IN AGGREGATED MICE

¹ Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire

The effects of drugs that modify the actions, metabolism or release of endogenous norepinephrine were studied on the toxicity of d-amphetamine in aggregated mice. Chlorpromazine, phenoxybenzamine and phenobarbital reduced the enhanced lethal and norepinephnine depleting effects of d-amphetamine in aggregated mice. Pretreatment with monoamine oxidase inhibitors, which increased the stores of endogenous norepinephrine, enhanced the toxicity, while pretreatment with agents that reduced the tissue stores of norepinephnine (reserpine, -methyl-m-tyrosine, syrosingopine and metaraminol) reduced the toxicity of d-amphetamine. These results are offered as further evidence that endogenous norepinephrine plays a role in the enhanced toxicity of d-amphetamine in aggregated mice.