In experiments on the isolated small intestine of the guinea‐pig, morphine inhibited the release of acetylcholine (ACh) into the bath fluid. Experimental evidence is presented which suggests that the reduced release of ACh could not be explained by an inhibition of the synthesis of ACh, nor by stabilization of the bound form of ACh in the tissue. Apparently morphine reduces the excitability of postganglionic structures and thereby the liberation of ACh from nerve endings during the process of excitation.

Morphine has a paralysing action on the peristaltic reflex in isolated guinea-pig ileum, as first demonstrated by Trendelenburg (1917). Recent work (Schaumann, Giovannini and Jochum, 1952;Schaumann, 1954) has shown that all strong analgesics have this property and that their po'ency on this preparation runs parallel to their analgesic power. The laevo isomers are much more active than the dextro isomers, both as analgesics and on the guinea-pig gut. Levorphan, which is the strongest analgesic, is also the most effective on the peristaltic reflex; its dextro isomer is inactive in both tests. These findings suggest that the analgesics exert their specific paralysing action by a mechanism analogous to that which is responsible for their analgesic effects. If so, the guinea-pig ileum would be a suitable preparation on which to study the mode of action of morphine and its substitutes.The present investigations were undertaken to determine the site of action of morphine on the guinea-pig ileum. Its paralysing activity was compared qualitatively and quantitatively with that of hexamethonium and atropine on the intestine stimulated by intraluminal pressure, nicotine, phenoxycholine, and acetylcholine. A few experiments were also done on the jejunum of the rabbit. METHODSGuinea-pigs or rabbits were killed by a blow on the neck. In the experiments on the guinea-pig the lower ileum was used, discarding the 10 cm. next to the caecum. A strip of jejunum was taken in the experiments on rabbits. The preparations were suspended in Mg-free Tyrode solution to which 0.3N-HCl was added to adjust the pH to 7.1-7.3. The bath was aerated with 95%/, 02 and 5% C02 and the temperature kept at 36-37°C.To elicit the peristaltic reflex the preparations were set up in a 45 ml. bath according to the method described by Trendelenburg (1917). Changes in volume, and isotonic contractions of the longitudinal *British Council Scholar. muscle, were recorded on a smoked drum. Peristaltic waves were elicited by a rise in intraluminal pressure of 1.5 or 2 cm. Tyrode solution. In some experiments the gut was stored in Tyrode solution at 5.50 C. for 24 hr., then suspended at 37' C. and allowed to recover for at least 1 hr. before the experiment was started. For distension of the lumen a pressure of 3 or 4 cm. of Tyrode solution was used in these tests. In normal and in cooled preparations the rise in intraluminal pressure was maintained for 1 min. and followed by a rest period of 2 min.Nicotine and phenoxycholine were added to the 45 ml. bath in doses of 30 or 45 j'g., washed out after 45 sec. and given every 3 min. Hexamethonium, atropine, and morphine were added 1 min. before a rise in intraluminal pressure or an application of nicotine or phenoxycholine; they were kept in the bath during several tests until their effect was maximal. The doses were increased from ineffective values in geometric steps of 1.5-2.0. The lowest dose was determined which inhibited peristaltic waves during a 1 min. rise in intraluminal pressure or reduced the contractions of...

It is commonly believed that the reflex fall in systemic blood pressure which results from electrical stimulation of the aortic nerve is due to excitation of the barosensory fibres. However, Douglas & Schaumann (1956) concluded from their experiments on the reflex effects of electrical stimulation of the cat's aortic nerve that this nerve must contain additional depressor afferents smaller than any barosensory fibres that have been recognized in it. These small afferents are not easily characterized in the cat because its aortic nerve is enclosed in the vagus throughout the greater part of its course. In the rabbit, on the other hand, the aortic nerve runs freely in the neck and is thus particularly suitable for experiments to correlate the reflex depressor effects obtained on stimulation of this nerve with its fibre components. Our study has revealed two distinct groups of afferents in the aortic nerve of the rabbit, both of which reflexly lower the blood pressure. The first group is composed of fastconducting fibres and contains the known barosensory afferents. The second group is made up of much smaller fibres which appear to be non-medullated, and whose reflex depressor effects are long-lasting and powerful. Non-medullated afferents have not previously been demonstrated in the buffer nerves.At present we do not know the nature of their receptors. METHODSAdult lop-eared rabbits were used and anaesthetized with 1-6-1-8 g/kg urethane given as a 25% solution into the marginal ear vein. Some animals required a further injection of the anaesthetic during the experiment. The right and left carotid arteries were tied, and the two vagi and both sympathetic nerves were sectioned. The right or left aortic nerve was identified as it joined one or other superior laryngeal nerve, and dissected downwards and cut a few centimetres from this junction. The freed nerve was placed on a pair of silver-silver chloride electrodes (about 3-4 mm inter-electrode distance) for stimulation, and kept in a liquid paraffin bath made by suitable * British Council Scholar.

17 patients with severe digoxin intoxication were successfully treated with 320 to 480 mg Fab fragments of digoxin-specific IgG from sheep. The infusion period ranged between 0.5 and 7 h. Serum and urine concentrations of digoxin bound to Fab fragments, and in 11 cases unbound Fab fragments in serum, were determined during and after the infusion. The renal clearance of bound digoxin and therefore of the antibody was 13.6 ml/min. The median extrarenal clearance of the Fab fragments was 10.9 ml/min. The half-life of the serum concentrations starting at 12 h was 14.3 h, and the value was increased to 25.4 h when regression began at 24 h; the corresponding apparent distribution volumes were 25.9 and 541. These figures exceed the volume of the extracellular space and suggest intracellular penetration of the Fab fragments. The dosage of the antibody should be sufficiently high to bind digoxin in the most severe cases of poisoning. The maximum serum concentrations of bound antibody were 30 mg/l after 3 h and 20 mg/l after 5 h. A loading dose of 160 mg followed by an infusion of 0.5 mg/min was sufficient to absorb digoxin re-diffusing into the serum during the first 8 h. In some cases free digoxin reappeared in the serum 8-12 h after beginning the treatment. This might be prevented by infusing a further ampoule at a rate of 0.1 mg/min or less.