Tissue levels of metaraminol and its metabolite, α-methylnorepinephrine,in control and 6-hydroxydopamine-pretreated guinea pigs |
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Authors: | Ray W Fuller Harold D Snoddy Kenneth W Perry |
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Institution: | The Lilly Research Laboratories, Eli Lilly and Company Indianapolis, Indiana 46285, U.S.A. |
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Abstract: | In guinea pigs, metaraminol disappeared from heart and liver during the first 4 days after its injection with a half-life of 31 and 30 hrs, respectively. In guinea pigs pretreated with 6-hydroxydopamine 24 hrs before metaraminol injection, tissue levels of metaraminol were lower, and the half-life was shortened to about 10 hrs in heart and 12 hrs in liver. Norepinephrine levels in 6-hydroxydopamine-treated guinea pigs were reduced by 93 percent in heart and 90 percent in liver, indicating nearly complete chemical sympathectomy in these tissues. α-Methylnorepinephrine, whose formation by guinea pig liver homogenates previously had been shown to occur unchanged after 6-hydroxydopamine treatment, was present in heart and liver at lower levels in 6-hydroxydopamine-pretreated guinea pigs than in controls. The half-life of α-methylnorepinephrine both in heart and in liver was 39 hrs in control guinea pigs. In 6-hydroxydopamine-pretreated guinea pigs, α-methylnorepinephrine disappeared too rapidly to permit half-life estimation. These data support the idea that metaraminol and α-methylnorepinephrine are retained in noradrenergic fibers and that this retention is a dominant factor in their rates of disappearance from tissues. |
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