The Effect of Nalorphine on the Antidiuretic Action of Morphine in Rats and Men

Abstract

In several mammalian species the diuretic response to water given by mouth is inhibited by morphine. De Bodo (1944) concluded, from experiments on dogs, that this inhibition cannot be attributed to the effect of morphine on water absorption from the gut; he suggested that it was due to release of posterior pituitary antidiuretic hormone.Nalorphine (N-allylnormorphine) antagonizes some of the pharmacological actions of morphine -for example, its effect on respiration (McCawley, Hart, and Marsh, 1941; Bodman, 1953) and its analgesic action (Unna, 1943;Hart and McCawley, 1944). It seemed of interest, therefore, to see whether nalorphine would antagonize the antidiuretic effect of morphine, and whether this could be achieved without affecting its analgesic action. METHODSEffects on renal water excretion in rats were tested by a method similar to that described by Ginsburg (1951). Adult male albino rats weighing approximately 200 g. were used. They were deprived of food for 16 hr. before the test, but were allowed free access to water. Each animal was then weighed, given water equivalent to 5 % of its body wt. by stomach tube and placed in a metabolism cage. One hr. later the animals were injected subcutaneously with the drug or drugs to be tested, and were again given water equivalent to 5% of their body wt. The volumes of urine excreted in the first hr. were noted. The "6 water load " of the animal at the beginning of the second hr. could thus be calculated. to a standard thermal stimulus until the rat moves its tail (Davies, Raventos, and Walpole, 1946). To avoid injury the animal's tail was never exposed to the stimulus for more than 20 sec.The water content of the rat brains was determined as follows. Two groups of adult male rats of 180-210 g. were treated as in the diuresis tests. One group was injected with 0.9% NaCl solution and the other with morphine sulphate (10 mg./kg.). At 0, 90, 180, and 270 min. after the injection, rats from both groups were quickly anaesthetized with ether and killed by bleeding. The brain was carefully dissected, placed on a weighed watchglass, and weighed. The cerebellum, cerebral hemispheres, medulla, and pons were immediately dissected from the basal nuclei and each of these pieces of brain weighed separately. The dissected brains were then dried.Water diuresis in man was investigated as follows: The subjects were deprived of food and fluids for 12 hr. before the test. They then emptied their bladders and had the drug or drugs injected intramuscularly. Immediately afterwards they drank a standard volume of water (860 ml./m.2 body surface).They lay on couches during the test, but were allowed to stand up to pass urine. In one instance a subject was not allowed to sit or stand during the test. Urine was collected at hourly intervals. Whenever possible cross-over experiments were performed with at least a week's interval between tests. All volunteers were unaware of what drug or drugs they received, and the drugs were given in a random manner. RESULTS Antidiuresis in Rats. -Fig. ...

Antidiuretic Effect of Morphine in the Rat: Tolerance and Physical Dependence

“…Renal haemodynamic changes (Papper & Papper, 1964), nervous influences (Lipschitz & Stokey, 1947), species differences (Inturrisi, May & Fujimoto, 1968), inhibition of water absorption from the gastrointestinal tract (Schnieden & Blackmore, 1955), urine retention in the bladder , changes in electrolytes and the use of hydrated and non-hydrated animals (for reference, see Fujimoto, 1971) may produce considerable changes in water distribution. However, if rats are previously loaded with water, morphine will produce a consistent antidiuretic response (Fujimoto, 1971).…”

Effect of Nicotine, Nornicotine and Allylnornicotine on the Diuretic Response to Water in Rats

“…Morphine antidiuresis can be antagonized by nalorphine, its N-allyl derivative (Winter, Gaffney & Flataker, 1954;Schnieden & Blackmore, 1955). The latter drug probably acts as a competitive antagonist.…”

The Effect of Levallorphan Tartrate and of Adiphenine Hydrochloride on the Antidiuretic Action of Morphine and Nicotine

“…Nalorphine has been shown to antagonize the antidiuretic effect of one of these compoundsnamely, morphine (Winter, Gaffney, and Flataker, 1954;Schnieden and Blackmore, 1955) and levallorphan is known to be a very potent antagonist of certain of the actions of morphine (Fromherz and Pellmont, 1952). It therefore seemed of interest to see if this latter compound antagonized the antidiuretic effects of both morphine and nicotine.…”