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The effects of physostigmine 1 mg i.v. were studied on the analgesia, sedation and reduction in respiratory rate induced by morphine 10 mg/60 kg i.v. in 10 patients recovering from surgery. Within 5-10 min, physostigmine abolished the somnolent effect of morphine and restored the respiratory rate to pre-drug values. Analgesia, assessed by an independent observer and by the patient was, if anything, increased by physostigmine. The analeptic effect of physostigmine lasted 40-60 min.

Isotopes of water (deuterium oxide and tritium oxide) have been used for the determination of total body water in certain mammalian species (Hevesy & Hofer, 1934;Pace, Kline, Schackman & Harfenist, 1947; Soberman, Brodie, Levy, Axelrod, Hollander & Steele, 1949;Haigh & Schnieden, 1956;Langham, Eversole, Hayes & Trujillo, 1956; Fallot, Aeberhardt & Masson, 1957). However, the techniques involved in these determinations have limited use, being either difficult, expensive or timeconsuming. Recent advances in scintillation counting techniques (Haigh, 1957) have made it much easier to estimate one of these isotopes of hydrogen, namely tritium. The purpose of the present paper is to describe how far such scintillation counter techniques can be applied to the determination of tritium in urine and plasma and the estimation of degree of error involved. The use of such techniques for a comparative study of total body water in a number of mammalian species and of water turnover under tropical conditions in one species, namely man, is also presented. METHODS 0-5 ml. of tritiated water or processed tritiated plasma or urine (see below) was added to 8 ml. of absolute ethanol and 10 ml. of scintillation solution (3 g 2:5-diphenyloxazole/l. sulphur-free toluene). The mixture was shaken and then centrifuged at approximately 1500 rev/min for 2-3 min. 5 ml. of the supernatant fluid was placed in the special counting container supplied with the N612 Ekco Scintillation Counter. This scintillation unit was kept at -20°C in a deep-freeze cabinet and its amplifier set at maximum gain. It was connected to a N 530E Ekco Automatic Scaler unit which was set at H.V. 1200 and Discrimator bias of -5 V. The scaler received a stabilized current from a constant-voltage stabilizer (Servomex AC 2 Mark IIB). Unless otherwise stated, all specimens were counted for 1000 sec and were allowed to cool in their counting containers for 1000 sec at -20°C before counting.Preparation of urine. 3*5 ml. of urine was mixed thoroughly in a test-tube with 0 5 g of activated charcoal. The resultant sludge was filtered through a Whatman No. 2 filter paper and 0 5 ml. of the filtrate was then added to 18 ml. of the alcohol-scintillator mixture, shaken and centrifuged, and a 5 ml. portion taken for counting. J. M. FOY AND H. SCHNIEDENPreparation of rat, cat, guinea-pig or rabbit plasma. 0*5 ml. of plasma was added to 18 ml. of the alcohol-scintillator solution mixture. After thorough shaking the mixture was centrifuged. 5 ml. of the clear supernatant fluid was then withdrawn and placed in the counting container before counting.Preparation of human plasma. Since it was found that the above method of preparation for rat plasma gave a coloured (orange-yellow) supernatant liquid with human and baboon plasma, another method was also investigated. The plasma was precipitated with 10 % trichloroacetic acid (Langham et al. 1956) and 0 5 ml. of the clear colourless filtrate was mixed with 18 ml. of alcohol-scintillation fluid mixture. 5 ml. of this final mixture was used f...

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Summary1. An investigation has been made of the effects of cadmium and zinc ions upon the contractile response of the guinea-pig isolated ileum to methacholine, histamine, potassium ion and a.c. field stimulation. The metal ions depress the response to all of these agents. 2. Radioisotope studies showed that cadmium and zinc ions have very much larger apparent volumes of distribution than sorbitol, both within whole ileum and within strips of the longitudinal smooth muscle layer. The results of these studies were indicative of surface binding and/or intracellular accumulation of these ions. 3. It is suggested that cadmium and zinc ions directly depress smooth muscle contractility in a non-specific manner. This action may result from their binding to or accumulation within the muscle cells.

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. ...

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Dopamine, apomorphine, noradrenaline and isoprenaline reduced the response of the isolated guinea-pig ileum to exogenous acetylcholine by a maximum of 40 %. Propranolol reversed this inhibition whilst phentolamine and pimozide were ineffective, suggesting that the drugs were acting on a post-synaptic 8-adrenoceptor. The same agonists were more effective as inhibitors of the response to transmural electrical stimulation of the ileum, lower doses producing almost complete inhibition. This inhibition was partially antagonized by phentolamine, pimozide and propranolol. Clonidine proved to be the most potent inhibitor of the response to transmural electrical stimulation, whilst phenylephrine was ineffective. PA, determinations showed that phentolamine was a potent antagonist of clonidine but a weak antagonist of apomorphine whilst for pimozide the opposite was true. The results suggest that there are two populations of prejunctional receptors on the cholinergic nerves innervating the smooth muscle of the guinea-pig ileum. One receptor is similar to a classical prejunctional a-adrenoceptor and the other resembles a central dopamine receptor.