NARCOTIC EFFECTS ON PHENOL RED DISPOSITION IN MICE

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Abstract
Morphine administration reduces phenol red clearance in mice. Increasing s.c. morphine doses from 10-40 mg/kg caused a progressive increase in plasma phenol red concentrations and reduced dye elimination in urine. I.v. phenol red given at 50-200 mg/kg was cleared from plasma at 24-30 .mu.l/min per kg body weight. At these dosages of dye, plasma clearance of phenol red was reduced at least 33% by morphine pretreatment (20 mg/kg s.c.). Lowered dye clearance by morphine was reflected in smaller apparent volumes of phenol red distribution. The morphine effect on the elimination constant (Kel) of phenol red was variable. The narcotic caused a rise in Kel at the lowest phenol red dose and lowered this constant at the high phenol red dose. Like morphine, hydromorphone and methadone had an antidiuretic effect in mice and reduced renal elimination of phenol red. Naloxone had no effect on phenol red disposition, but completely reversed the effect of morphine. The effect of the narcotic was not due to competition or displacement from transport sites. Morphine did not cause a change in urine pH. As the urine did not become more acidic after morphine, back diffusion of undissociated dye is not likely as the cause of its reduced renal elimination. Reduced renal elimination of phenol red by narcotics is probably due to reduced renal blood flow and glomerular filtration as shown by lowered p-aminohippurate and iothalamate clearance in mice.