Harold Blumberg

USE OF WRITHING TEST FOR EVALUATING ANALGESIC ACTIVITY OF NARCOTIC ANTAGONISTS.

Summary In a comparison of 6 narcotic antagonists, the analgesic potencies found on the phenylquinone writhing test, in both mice and rats, roughly paralleled the analgesic potencies reported in man. The analgesic potencies did not correlate with the narcotic antagonist potencies. In view of the fact that the narcotic antagonist analgesics are inactive on the usual analgesic tests in animals, it appears that the writhing test may be a valuable aid in attempting to predict the analgesic activity of narcotic antagonists in man.

Counteraction of Narcotic Antagonist Analgesics by the Narcotic Antagonist Naloxone

Summary When the potent narcotic antagonist, naloxone, was injected subcutane-ously into mice and rats simultaneously with narcotic antagonist analgesics, naloxone counteracted the writhing test analgesic activity of the antagonists. Naloxone completely antagonized the potent analgesic activity of pentazocine, nalorphine, cyclazocine, and cy-clorphan, and also antagonized the weak analgesic activity of levallorphan.

High activity of potent analgesics on conditioned rat tranquilizer test.

Summary The analgesics codeine, morphine, and l-14-hydroxydihydromorphinone (Numorphan) produced inhibition of the conditioned avoidance-escape response in rats, a widely used tranquilizer test. The potencies in blocking conditioned response correlated roughly with analgesic potencies. The very potent analgesic, l-14-hydroxydihydromorphinone, exhibited by subcutaneous injection slightly more conditioned response blocking activity than perphenazine, one of the most active tranquilizers now in clinical use.

Adenomatous stomach lesion of the rat associated with heavy Cysticercus fasciolaris infestation.

Summary The production of adenomatous stomach lesions of the rat, associated with heavy liver infestations of Cysticercus fasciolaris, is reported. The adenomatous stomach lesions have been produced in 3 different strains of rats.

Emulsification of Fat for Intravenous Administration

Conclusion Supersonic radiation appears to be the most suitable method yet studied for preparing fat emulsions, suitable for intravenous use in man. An emulsion of fat that could safely be given in quantity by vein was first developed by Yamakawa and his collaborators 1 in Japan. Recent observations in Latin America and in this country 2 have confirmed and extended their work and have furnished very suggestive clinical and experimental evidence of the value of such preparations. The technique used by Japanese and American workers is essentially similar: the fat or oil is mixed with purified egg lecithin (Mercks or Kahlbaums) and water and passed through a 2-stage dairy homogenizer operating at 3000 to 4000 lb. pressure, after which the product is sterilized by heat in sealed containers. When suitable quantities are used, it is possible to obtain an emulsion in which practically all the lecithin-coated fat globules are less than 2μ in diameter with only an occasional one as large as 3 or 3.5μ. Such an emulsion passes through the lung capillaries with ease, 3 avoiding the danger of fat embolism, which may occur when the particles exceed 4μ in diameter. 4 A difficulty that has been experienced—both with Japanese and American preparations—is the limited time during which these emulsions are stable. In the course of a few weeks, more or less, the larger fat particles which are in less active Brownian movement tend to rise to the surface, forming a visible cream layer. Although the formation of the cream does not necessarily indicate an increased particle size, nevertheless the large fat particles are in close apposition, and there is danger of their coalescing to form larger aggregates.

Effect of Warfarin (Coumadin) Sodium Administration During Lactation on Blood Coagulation of Nursling Rats.

Summary When a therapeutic dosage of the anticoagulant warfarin (Coumadin) sodium was fed to lactating rats, there was no effect on whole blood clotting time of the nurslings, or on their subsequent growth and reproduction. When toxic or lethal levels of warfarin sodium were fed to the mothers, clotting time was prolonged in the nurslings. This demonstrated that the anticoagulant effect could be transmitted through the milk when mothers received toxic dosages. However, at all dosages the anticoagulant effect was much less in nurslings than in mothers.