ACCORDING TO Arena,1 and Krimmel and Sunshine,2 more than 500,000 cases of poisoning occur each year in this country, with about 1,500 resultant deaths. Arena1 states that the number of child deaths from accidental poisoning exceeds the total number of deaths caused by measles, polio, scarlet fever, and diphtheria. In many types of poisoning the primary step in treatment is to evacuate the stomach.Berry and Lambdin3 point out that one of two methods is generally employed for emptying the stomach of toxic material; stomach lavage or pharmacologically-induced emesis. There are differences of opinion as to which is the best method: Robertson4 suggested the use of syrup of ipecac, Berry and Lambdin3 prefer apomorphine hydrochloride (HCl), while Arnold et al5 found that stomach lavage is less effective than syrup of ipecac.Since there seems to be no general agreement as to which is the best emetic, nor indeed as to whether emesis or gastric lavage is the better method for emptying the stom¬ ach, we believed it would be worthwhile to investigate quantitatively in animals the stomach-emptying effect of these agents as measured by percentage recovery of a test meal of barium sulfate. We decided to thus compare the effects of the emetic drugs, syr¬ up of ipecac, apomorphine HCl and lobeline sulfate (SO4) and those of gastric la¬ vage.We decided first to determine the minimal dose of apomorphine HCl, syrup of ipecac, and lobeline S04 which would induce emesis in 100% of our animals; and then to estab¬ lish an "optimal emetic dose" of each drug (based on ability to recover barium sulfate).We then determined the effect of the time interval between ingestion and treatment on the percentage of barium sulfate recovered by the optimal emetic dose of the above mentioned drugs, or stomach lavage. Methods and MaterialsColorimetrie Assay of Barium Sulfate.-The method which was employed in this analysis was a modified combination of the method of the United States Pharmacopeia,® and that of Frediani and Bablee.7 The method was as fol¬ lows: 15 gm of the vomitus was mixed with 4 gm of anhydrous potassium carbonate and the mixture heated in a crucible at 750 C until fu¬ sion was completed. The residue was washed with distilled water, dissolved in acetic acid and the barium was assayed as described by Fredi¬ ani and Bablee.Determination of the Optimal Emetic Doses.-First we determined the lowest dose of apo¬ morphine HCl that caused 100% emetic re¬ sponse in the young dog. This dose was found to be 0.15 mg/kg, subcutaneously (SC). The 100% emetic dose being determined, we pro-
Widespread use and abuse of barbiturates has resulted in numerous cases of barbiturate poisoning. Usually victims of barbiturate overdose are given supportive care while diuresis, dialysis, and gastrointestinal adsorption are used to lower barbiturate blood levels. Unfortunately, there is no specific antagonist for use in barbiturate poisoning, although some investigators have advocated the use of powerful analeptic agents ( 1 , 2) for shortening narcosis. Present knowledge views the antagonistic action of analeptics as the result of nonspecific central nervous system stimulation. In deep coma the difference between the lowest dose of analeptic producing a discernible effect and that producing convulsions may be very small (3). Also, at high doses the analeptics often produce vomiting and cardiac arrhythmias (5, 6).This report deals with 2 (3,4-dichlorophenoxy) methyl-2-imidazoline (DH-524) 11 an agent which shares with known analeptics the property of dramatically shortening barbiturate narcosis.2 However, several important differences between DH-524 and a typical analeptic, bemegride, were discovered in these studies.Materials and Methods. Male albino mice (Spartan strain Swiss Webster) from Spartan Research Animals, Inc. (Haslett, MI) were used in all studies. Animals of approximately the same age and weight were used in each experiment. Sleeping times were defined as the time from the ip injection of depressant until the animal was able to right him-1The details of the preparation and purification of the DH-524 used in this study are reported in U S . Pat. No. 3449355. 2Unpublishjed data, A. D. Rudzik and J. H. Mennear in this hboratary.self twice. In each experiment narcosis was allowed to develop for 10 min after injection of the depressant, and then iv injections of Krebs buffer or test drugs dissolved in Krebs were given. Animals which were not asleep at the time of iv injection were eliminated from the experiment. Because there was considerable day to day variation in sleeping times, each experiment contained a control group which received only depressant and iv Krebs. Drug groups were then compared to their own controls by use of Student's t test.Spontaneous motor activity measurements were obtained from individual animals with an electronic activity monitor (Stoelting Co.).Mice were placed in plastic cages ( 1 1 X 13x 8 cm) for a 30 min acclimitization period during which no measurements were made. Subsequently pretreatment activity was recorded for 30 min and then drugs were administered. Recording of activity was continued for three 30 min periods. Since these experiments extended over a period of days in order to accumulate sufficient data, the effect of diurnal variation was distributed equally among the treatment groups (10 mice/group) by simultaneously testing one member from each group at each session.Convulsant activity was determined by continuous iv infusion of 5 mg/ml solutions of drug. Ten mice were used for each group, with a weight range of 27-34 g. All animals received the drug solutions...
Aus den Phenolen (I) und Chloracetonitril (II) entstehen die Äther (III), die über die Iminoäther (IV) weiter umgesetzt werden.
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