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      Pharmacokinetics, plasma protein binding and urinary excretion of Nω-nitro-L-arginine in rats

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      British Journal of Pharmacology
      Wiley

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          Blockade of tolerance to morphine but not to kappa opioids by a nitric oxide synthase inhibitor.

          The nitric oxide synthase inhibitor NG-nitro-L-arginine (NO2Arg) blocks morphine tolerance in mice. After implantation of morphine pellets the analgesic response decreases from 100% on the first day to 0% on the third. Coadministration of NO2Arg along with the pellets markedly retards the development of tolerance; 60% of mice are analgesic after 3 days, and 50% of mice are analgesic after 5 days. In a daily injection paradigm the analgesic response to morphine is reduced from 60% to 0% by 5 days. Concomitant administration of morphine along with NO2Arg at doses of 2 mg/kg per day prevents tolerance for 4 weeks. A single NO2Arg dose retards morphine tolerance for several days, and dosing every 4 days is almost as effective as daily NO2Arg. NO2Arg slowly reverses preexisting tolerance over 5 days despite the continued administration of morphine along with NO2Arg. NO2Arg also reduces dependence and reverses previously established dependence. NO2Arg does not prevent tolerance to analgesia mediated by the kappa 1 agonist trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolindinyl)cyclohexyl]- benzene-acetamide (U50,488H) or the kappa 3 agent naloxone benzoylhydrazone, indicating a selective action of NO in the mechanisms of mu tolerance and dependence.
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            Overproduction of nitric oxide in cytokine-mediated and septic shock.

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              LAGRAN program for area and moments in pharmacokinetic analysis.

              A computer program is described for examination of areas (AUC) and moments of serum concentration vs time data using the Lagrange technique alone or in conjunction with linear or log-trapezoidal methods. The suitability of the Lagrange polynomial approximations to the experimental data during AUC computation is possible through output of interpolated values between consecutive data points. Ill-fitting AUC's between any data points can be replaced with values generated by either trapezoidal method. Along with the partial and total AUC and moment, the program generates model-independent pharmacokinetic parameters such as plasma clearance, terminal slope, half-life, volume of distribution at steady-state, mean residence time, and variance of the residence time.
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                Author and article information

                Journal
                British Journal of Pharmacology
                Wiley
                00071188
                February 1994
                February 1994
                July 19 2012
                : 111
                : 2
                : 394-396
                Article
                10.1111/j.1476-5381.1994.tb14747.x
                3e7d0329-e136-4e36-aeb2-897c7c58a2ff
                © 2012

                http://doi.wiley.com/10.1002/tdm_license_1.1

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