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The present study determined the effect of organically quaternizing either of the two tertiary nitrogen sites of nicotine to assess the in vivo effects of the permanently ionized states of the synthesized N-[14C]methylnicotines on brain uptake in rat after intracarotid injection. Male Sprague-Dawley rats were used to measure the brain uptake index (BUI) by single-pass clearance in brain after rapid injection at pH 7.4 into the left common carotid artery (expressed as a percentage) relative to simultaneously injected 3HOH. The BUI of [14C]mannitol, a control for the method background, was measured to be 2.6 +/- 0.6. At physiological pH, in striking contrast to the [pyrrolidine-2-14C]nicotine BUI of 120 +/- 3, the N-[14C]-methylnicotines had a BUI of 3.0 +/- 0.6, which was not significantly different from the method background and which indicated abolition of blood-brain barrier penetration of nicotine with the sensitivity of the BUI method.
W H Oldendorf, and
B E Stoller, and
F L Harris
July 2011,
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W H Oldendorf, and
B E Stoller, and
F L Harris
January 1992,
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W H Oldendorf, and
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F L Harris
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W H Oldendorf, and
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W H Oldendorf, and
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F L Harris
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W H Oldendorf, and
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W H Oldendorf, and
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F L Harris
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Expert opinion on drug discovery,
W H Oldendorf, and
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Therapeutic delivery,
W H Oldendorf, and
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F L Harris
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Chinese medical journal,
W H Oldendorf, and
B E Stoller, and
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July 1967,
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